Cancer-associated fibroblasts as key regulators of the breast cancer tumor microenvironment

1.

Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646–674. https://doi.org/10.1016/j.cell.2011.02.013.CrossRefPubMed

2.

Bainbridge, P. (2013). Wound healing and the role of fibroblasts. Journal of Wound Care, 22(8), 407–408, 410-412. https://doi.org/10.12968/jowc.2013.22.8.407.CrossRefPubMed

3.

Kalluri. (2016). The biology and function of fibroblasts in cancer. Nature, 16(9), 582–598.

4.

Unsworth, A., Anderson, R., & Britt, K. (2014). Stromal fibroblasts and the immune microenvironment: partners in mammary gland biology and pathology? Journal of Mammary Gland Biology and Neoplasia, 19(2), 169–182. https://doi.org/10.1007/s10911-014-9326-8.CrossRefPubMed

5.

Visvader, J. E., & Stingl, J. (2014). Mammary stem cells and the differentiation hierarchy: current status and perspectives. Genes & Development, 28(11), 1143–1158. https://doi.org/10.1101/gad.242511.114.CrossRef

6.

Polyak, K., & Kalluri, R. (2010). The role of the microenvironment in mammary gland development and cancer. Cold Spring Harbor Perspectives in Biology, 2(11), a003244. https://doi.org/10.1101/cshperspect.a003244.CrossRefPubMedPubMedCentral

7.

Fleming, J. M., Long, E. L., Ginsburg, E., Gerscovich, D., Meltzer, P. S., & Vonderhaar, B. K. (2008). Interlobular and intralobular mammary stroma: genotype may not reflect phenotype. BMC Cell Biology, 9, 46. https://doi.org/10.1186/1471-2121-9-46.CrossRefPubMedPubMedCentral

8.

Morsing, M., Klitgaard, M. C., Jafari, A., Villadsen, R., Kassem, M., Petersen, O. W., et al. (2016). Evidence of two distinct functionally specialized fibroblast lineages in breast stroma. Breast Cancer Research, 18(1), 108. https://doi.org/10.1186/s13058-016-0769-2.CrossRefPubMedPubMedCentral

9.

Inman, J. L., Robertson, C., Mott, J. D., & Bissell, M. J. (2015). Mammary gland development: cell fate specification, stem cells and the microenvironment. Development, 142(6), 1028–1042. https://doi.org/10.1242/dev.087643.CrossRefPubMed

10.

Bussard, K. M., Mutkus, L., Stumpf, K., Gomez-Manzano, C., & Marini, F. C. (2016). Tumor-associated stromal cells as key contributors to the tumor microenvironment. Breast Cancer Research, 18(1), 84. https://doi.org/10.1186/s13058-016-0740-2.CrossRefPubMedPubMedCentral

11.

Osterreicher, C. H., Penz-Osterreicher, M., Grivennikov, S. I., Guma, M., Koltsova, E. K., Datz, C., et al. (2011). Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver. Proceedings of the National Academy of Sciences of the United States of America, 108(1), 308–313. https://doi.org/10.1073/pnas.1017547108.CrossRefPubMed

12.

Lv, F. J., Tuan, R. S., Cheung, K. M., & Leung, V. Y. (2014). Concise review: the surface markers and identity of human mesenchymal stem cells. Stem Cells, 32(6), 1408–1419. https://doi.org/10.1002/stem.1681.CrossRefPubMed

13.

Meng, M. B., Zaorsky, N. G., Deng, L., Wang, H. H., Chao, J., Zhao, L. J., et al. (2015). Pericytes: a double-edged sword in cancer therapy. Future Oncology, 11(1), 169–179. https://doi.org/10.2217/fon.14.123.CrossRefPubMed

14.

Su, S., Chen, J., Yao, H., Liu, J., Yu, S., Lao, L., et al. (2018). CD10(+)GPR77(+) cancer-associated fibroblasts promote cancer formation and chemoresistance by sustaining cancer stemness. Cell, 172(4), 841–856.e816. https://doi.org/10.1016/j.cell.2018.01.009.CrossRefPubMed

15.

Brechbuhl, H. M., Finlay-Schultz, J., Yamamoto, T. M., Gillen, A. E., Cittelly, D. M., Tan, A. C., et al. (2017). Fibroblast subtypes regulate responsiveness of luminal breast cancer to estrogen. Clinical Cancer Research, 23(7), 1710–1721. https://doi.org/10.1158/1078-0432.ccr-15-2851.CrossRefPubMed

16.

Tchou, J., Kossenkov, A. V., Chang, L., Satija, C., Herlyn, M., Showe, L. C., et al. (2012). Human breast cancer associated fibroblasts exhibit subtype specific gene expression profiles. BMC Medical Genomics, 5, 39–39. https://doi.org/10.1186/1755-8794-5-39.CrossRefPubMedPubMedCentral

17.

Busch, S., Andersson, D., Bom, E., Walsh, C., Stahlberg, A., & Landberg, G. (2017). Cellular organization and molecular differentiation model of breast cancer-associated fibroblasts. Molecular Cancer, 16(1), 73. https://doi.org/10.1186/s12943-017-0642-7.CrossRefPubMedPubMedCentral

18.

Jotzu, C., Alt, E., Welte, G., Li, J., Hennessy, B. T., Devarajan, E., et al. (2011). Adipose tissue derived stem cells differentiate into carcinoma-associated fibroblast-like cells under the influence of tumor derived factors. Cellular Oncology (Dordrecht), 34(1), 55–67. https://doi.org/10.1007/s13402-011-0012-1.CrossRef

19.

Cho, J. A., Park, H., Lim, E. H., & Lee, K. W. (2012). Exosomes from breast cancer cells can convert adipose tissue-derived mesenchymal stem cells into myofibroblast-like cells. International Journal of Oncology, 40(1), 130–138. https://doi.org/10.3892/ijo.2011.1193.CrossRefPubMed

20.

Weber, C. E., Kothari, A. N., Wai, P. Y., Li, N. Y., Driver, J., Zapf, M. A., et al. (2015). Osteopontin mediates an MZF1-TGF-beta1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer. Oncogene, 34(37), 4821–4833. https://doi.org/10.1038/onc.2014.410.CrossRefPubMed

21.

Avgustinova, A., Iravani, M., Robertson, D., Fearns, A., Gao, Q., Klingbeil, P., et al. (2016). Tumour cell-derived Wnt7a recruits and activates fibroblasts to promote tumour aggressiveness. Nature Communications, 7, 10305. https://doi.org/10.1038/ncomms10305.CrossRefPubMedPubMedCentral

22.

Chen, J. Y., Li, C. F., Kuo, C. C., Tsai, K. K., Hou, M. F., & Hung, W. C. (2014). Cancer/stroma interplay via cyclooxygenase-2 and indoleamine 2,3-dioxygenase promotes breast cancer progression. Breast Cancer Research, 16(4), 410. https://doi.org/10.1186/s13058-014-0410-1.CrossRefPubMedPubMedCentral

23.

Mishra, P. J., Mishra, P. J., Humeniuk, R., Medina, D. J., Alexe, G., Mesirov, J. P., et al. (2008). Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Research, 68(11), 4331–4339. https://doi.org/10.1158/0008-5472.can-08-0943.CrossRefPubMedPubMedCentral

24.

Kidd, S., Spaeth, E., Watson, K., Burks, J., Lu, H., Klopp, A., et al. (2012). Origins of the tumor microenvironment: quantitative assessment of adipose-derived and bone marrow-derived stroma. PLoS One, 7(2), e30563. https://doi.org/10.1371/journal.pone.0030563.CrossRefPubMedPubMedCentral

25.

Dirat, B., Bochet, L., Dabek, M., Daviaud, D., Dauvillier, S., Majed, B., et al. (2011). Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Research, 71(7), 2455–2465. https://doi.org/10.1158/0008-5472.can-10-3323.CrossRefPubMed

26.

Bochet, L., Lehuede, C., Dauvillier, S., Wang, Y. Y., Dirat, B., Laurent, V., et al. (2013). Adipocyte-derived fibroblasts promote tumor progression and contribute to the desmoplastic reaction in breast cancer. Cancer Research, 73(18), 5657–5668. https://doi.org/10.1158/0008-5472.can-13-0530.CrossRefPubMed

27.

Kojima, Y., Acar, A., Eaton, E. N., Mellody, K. T., Scheel, C., Ben-Porath, I., et al. (2010). Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proceedings of the National Academy of Sciences of the United States of America, 107(46), 20009–20014. https://doi.org/10.1073/pnas.1013805107.CrossRefPubMedPubMedCentral

28.

Nair, N., Calle, A. S., Zahra, M. H., Prieto-Vila, M., Oo, A. K. K., Hurley, L., et al. (2017). A cancer stem cell model as the point of origin of cancer-associated fibroblasts in tumor microenvironment. Scientific Reports, 7(1), 6838. https://doi.org/10.1038/s41598-017-07144-5.CrossRefPubMedPubMedCentral

29.

LeBleu, V. S., Taduri, G., O'Connell, J., Teng, Y., Cooke, V. G., Woda, C., et al. (2013). Origin and function of myofibroblasts in kidney fibrosis. Nature Medicine, 19(8), 1047–1053. https://doi.org/10.1038/nm.3218.CrossRefPubMedPubMedCentral

30.

Zarzynska, J. M. (2014). Two faces of TGF-beta1 in breast cancer. Mediators of Inflammation, 2014, 141747. https://doi.org/10.1155/2014/141747.CrossRefPubMedPubMedCentral

31.

Kakarla, S., Song, X.-T., & Gottschalk, S. (2012). Cancer-associated fibroblasts as targets for immunotherapy. Immunotherapy, 4(11), 1129–1138. https://doi.org/10.2217/imt.12.112.CrossRefPubMed

32.

Shangguan, L., Ti, X., Krause, U., Hai, B., Zhao, Y., Yang, Z., et al. (2012). Inhibition of TGF-beta/Smad signaling by BAMBI blocks differentiation of human mesenchymal stem cells to carcinoma-associated fibroblasts and abolishes their protumor effects. Stem Cells, 30(12), 2810–2819. https://doi.org/10.1002/stem.1251.CrossRefPubMed

33.

Gao, M. Q., Kim, B. G., Kang, S., Choi, Y. P., Yoon, J. H., & Cho, N. H. (2013). Human breast cancer-associated fibroblasts enhance cancer cell proliferation through increased TGF-alpha cleavage by ADAM17. Cancer Letters, 336(1), 240–246. https://doi.org/10.1016/j.canlet.2013.05.011.CrossRefPubMed

34.

Guido, C., Whitaker-Menezes, D., Capparelli, C., Balliet, R., Lin, Z., Pestell, R. G., et al. (2012). Metabolic reprogramming of cancer-associated fibroblasts by TGF-beta drives tumor growth: connecting TGF-beta signaling with "Warburg-like" cancer metabolism and L-lactate production. Cell Cycle, 11(16), 3019–3035. https://doi.org/10.4161/cc.21384.CrossRefPubMedPubMedCentral

35.

Martinez-Outschoorn, U. E., Prisco, M., Ertel, A., Tsirigos, A., Lin, Z., Pavlides, S., et al. (2011). Ketones and lactate increase cancer cell "stemness," driving recurrence, metastasis and poor clinical outcome in breast cancer: achieving personalized medicine via Metabolo-Genomics. Cell Cycle, 10(8), 1271–1286. https://doi.org/10.4161/cc.10.8.15330.CrossRefPubMedPubMedCentral

36.

Zhang, D., Wang, Y., Shi, Z., Liu, J., Sun, P., Hou, X., et al. (2015). Metabolic reprogramming of cancer-associated fibroblasts by IDH3alpha downregulation. Cell Reports, 10(8), 1335–1348. https://doi.org/10.1016/j.celrep.2015.02.006.CrossRefPubMed

37.

Yan, W., Wu, X., Zhou, W., Fong, M. Y., Cao, M., Liu, J., et al. (2018). Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells. Nature Cell Biology, 20(5), 597–609. https://doi.org/10.1038/s41556-018-0083-6.CrossRefPubMedPubMedCentral

38.

Donnarumma, E., Fiore, D., Nappa, M., Roscigno, G., Adamo, A., Iaboni, M., et al. (2017). Cancer-associated fibroblasts release exosomal microRNAs that dictate an aggressive phenotype in breast cancer. Oncotarget, 8(12), 19592–19608. https://doi.org/10.18632/oncotarget.14752.CrossRefPubMedPubMedCentral

39.

Reya, T., Morrison, S. J., Clarke, M. F., & Weissman, I. L. (2001). Stem cells, cancer, and cancer stem cells. Nature, 414(6859), 105–111. https://doi.org/10.1038/35102167.CrossRefPubMed

40.

Peiris-Pages, M., Sotgia, F., & Lisanti, M. P. (2015). Chemotherapy induces the cancer-associated fibroblast phenotype, activating paracrine Hedgehog-GLI signalling in breast cancer cells. Oncotarget, 6(13), 10728–10745. https://doi.org/10.18632/oncotarget.3828.CrossRefPubMedPubMedCentral

41.

Zhao, X. L., Lin, Y., Jiang, J., Tang, Z., Yang, S., Lu, L., et al. (2017). High-mobility group box 1 released by autophagic cancer-associated fibroblasts maintains the stemness of luminal breast cancer cells. The Journal of Pathology, 243(3), 376–389. https://doi.org/10.1002/path.4958.CrossRefPubMed

42.

Tsuyada, A., Chow, A., Wu, J., Somlo, G., Chu, P., Loera, S., et al. (2012). CCL2 mediates cross-talk between cancer cells and stromal fibroblasts that regulates breast cancer stem cells. Cancer Research, 72(11), 2768–2779. https://doi.org/10.1158/0008-5472.can-11-3567.CrossRefPubMedPubMedCentral

43.

Cazet, A. S., Hui, M. N., Elsworth, B. L., Wu, S. Z., Roden, D., Chan, C. L., et al. (2018). Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer. Nature Communications, 9(1), 2897. https://doi.org/10.1038/s41467-018-05220-6.CrossRefPubMedPubMedCentral

44.

Boesch, M., Onder, L., Cheng, H.-W., Novkovic, M., Mörbe, U., Sopper, S., et al. (2018). Interleukin 7-expressing fibroblasts promote breast cancer growth through sustenance of tumor cell stemness. OncoImmunology, 7(4), e1414129. https://doi.org/10.1080/2162402X.2017.1414129.CrossRefPubMedPubMedCentral

45.

Sansone, P., Savini, C., Kurelac, I., Chang, Q., Amato, L. B., Strillacci, A., et al. (2017). Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer. Proceedings of the National Academy of Sciences of the United States of America, 114(43), E9066–e9075. https://doi.org/10.1073/pnas.1704862114.CrossRefPubMedPubMedCentral

46.

De Wever, O., Van Bockstal, M., Mareel, M., Hendrix, A., & Bracke, M. (2014). Carcinoma-associated fibroblasts provide operational flexibility in metastasis. Seminars in Cancer Biology, 25, 33–46. https://doi.org/10.1016/j.semcancer.2013.12.009.CrossRefPubMed

47.

Dittmer, A., & Dittmer, J. (2018). Long-term exposure to carcinoma-associated fibroblasts makes breast cancer cells addictive to integrin beta1. Oncotarget, 9(31), 22079–22094. https://doi.org/10.18632/oncotarget.25183.CrossRefPubMedPubMedCentral

48.

Orimo, A., Gupta, P. B., Sgroi, D. C., Arenzana-Seisdedos, F., Delaunay, T., Naeem, R., et al. (2005). Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell, 121(3), 335–348. https://doi.org/10.1016/j.cell.2005.02.034.CrossRefPubMed

49.

Al-Rakan, M. A., Colak, D., Hendrayani, S. F., Al-Bakheet, A., Al-Mohanna, F. H., Kaya, N., et al. (2013). Breast stromal fibroblasts from histologically normal surgical margins are pro-carcinogenic. The Journal of Pathology, 231(4), 457–465. https://doi.org/10.1002/path.4256.CrossRefPubMed

50.

Chen, L. C., Tu, S. H., Huang, C. S., Chen, C. S., Ho, C. T., Lin, H. W., et al. (2012). Human breast cancer cell metastasis is attenuated by lysyl oxidase inhibitors through down-regulation of focal adhesion kinase and the paxillin-signaling pathway. Breast Cancer Research and Treatment, 134(3), 989–1004. https://doi.org/10.1007/s10549-012-1986-8.CrossRefPubMed

51.

Tyan, S. W., Hsu, C. H., Peng, K. L., Chen, C. C., Kuo, W. H., Lee, E. Y., et al. (2012). Breast cancer cells induce stromal fibroblasts to secrete ADAMTS1 for cancer invasion through an epigenetic change. PLoS One, 7(4), e35128. https://doi.org/10.1371/journal.pone.0035128.CrossRefPubMedPubMedCentral

52.

Pinto, M. P., Dye, W. W., Jacobsen, B. M., & Horwitz, K. B. (2014). Malignant stroma increases luminal breast cancer cell proliferation and angiogenesis through platelet-derived growth factor signaling. BMC Cancer, 14, 735. https://doi.org/10.1186/1471-2407-14-735.CrossRefPubMedPubMedCentral

53.

Adams, E. F., Newton, C. J., Braunsberg, H., Shaikh, N., Ghilchik, M., & James, V. H. (1988). Effects of human breast fibroblasts on growth and 17 beta-estradiol dehydrogenase activity of MCF-7 cells in culture. Breast Cancer Research and Treatment, 11(2), 165–172.CrossRefPubMed

54.

Cheng, G., Fan, X., Hao, M., Wang, J., Zhou, X., & Sun, X. (2016). Higher levels of TIMP-1 expression are associated with a poor prognosis in triple-negative breast cancer. Molecular Cancer, 15(1), 30. https://doi.org/10.1186/s12943-016-0515-5.CrossRefPubMedPubMedCentral

55.

Rasmussen, A. A., & Cullen, K. J. (1998). Paracrine/autocrine regulation of breast cancer by the insulin-like growth factors. Breast Cancer Research and Treatment, 47(3), 219–233.CrossRefPubMed

56.

Bernard, S., Myers, M., Fang, W. B., Zinda, B., Smart, C., Lambert, D., et al. (2018). CXCL1 derived from mammary fibroblasts promotes progression of mammary lesions to invasive carcinoma through CXCR2 dependent mechanisms. Journal of Mammary Gland Biology and Neoplasia. https://doi.org/10.1007/s10911-018-9407-1.

57.

Jin, K., Pandey, N. B., & Popel, A. S. (2017). Crosstalk between stromal components and tumor cells of TNBC via secreted factors enhances tumor growth and metastasis. Oncotarget, 8(36), 60210–60222. https://doi.org/10.18632/oncotarget.19417.CrossRefPubMedPubMedCentral

58.

Pickup, M. W., Mouw, J. K., & Weaver, V. M. (2014). The extracellular matrix modulates the hallmarks of cancer. EMBO Reports, 15(12), 1243–1253. https://doi.org/10.15252/embr.201439246.CrossRefPubMedPubMedCentral

59.

Bergamaschi, A., Tagliabue, E., Sørlie, T., Naume, B., Triulzi, T., Orlandi, R., et al. (2008). Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome. The Journal of Pathology, 214(3), 357–367. https://doi.org/10.1002/path.2278.CrossRefPubMed

60.

Robertson, C. (2016). The extracellular matrix in breast cancer predicts prognosis through composition, splicing, and crosslinking. Experimental Cell Research, 343(1), 73–81. https://doi.org/10.1016/j.yexcr.2015.11.009.CrossRefPubMed

61.

Boraschi-Diaz, I., Wang, J., Mort, J. S., & Komarova, S. V. (2017). Collagen type I as a ligand for receptor-mediated signaling. [Review]. Frontiers in Physics, 5(12). https://doi.org/10.3389/fphy.2017.00012.

62.

Heino, J. (2014). Cellular signaling by collagen-binding integrins. Advances in Experimental Medicine and Biology, 819, 143–155. https://doi.org/10.1007/978-94-017-9153-3_10.CrossRefPubMed

63.

Bhogal, R. K., Stoica, C. M., McGaha, T. L., & Bona, C. A. (2005). Molecular aspects of regulation of collagen gene expression in fibrosis. Journal of Clinical Immunology, 25(6), 592–603. https://doi.org/10.1007/s10875-005-7827-3.CrossRefPubMed

64.

Bates, A. L., Pickup, M. W., Hallett, M. A., Dozier, E. A., Thomas, S., & Fingleton, B. (2015). Stromal matrix metalloproteinase 2 regulates collagen expression and promotes the outgrowth of experimental metastases. The Journal of Pathology, 235(5), 773–783. https://doi.org/10.1002/path.4493.CrossRefPubMed

65.

Kim, S. H., Lee, H. Y., Jung, S. P., Kim, S., Lee, J. E., Nam, S. J., et al. (2014). Role of secreted type I collagen derived from stromal cells in two breast cancer cell lines. Oncology Letters, 8(2), 507–512. https://doi.org/10.3892/ol.2014.2199.CrossRefPubMedPubMedCentral

66.

Liu, J., Shen, J. X., Wu, H. T., Li, X. L., Wen, X. F., Du, C. W., et al. (2018). Collagen 1A1 (COL1A1) promotes metastasis of breast cancer and is a potential therapeutic target. Discovery Medicine, 25(139), 211–223.PubMed

67.

Krishnamachary, B., Stasinopoulos, I., Kakkad, S., Penet, M. F., Jacob, D., Wildes, F., et al. (2017). Breast cancer cell cyclooxygenase-2 expression alters extracellular matrix structure and function and numbers of cancer associated fibroblasts. Oncotarget, 8(11), 17981–17994. https://doi.org/10.18632/oncotarget.14912.CrossRefPubMedPubMedCentral

68.

Badaoui, M., Mimsy-Julienne, C., Saby, C., Van Gulick, L., Peretti, M., Jeannesson, P., et al. (2018). Collagen type 1 promotes survival of human breast cancer cells by overexpressing Kv10.1 potassium and Orai1 calcium channels through DDR1-dependent pathway. Oncotarget, 9(37), 24653–24671. https://doi.org/10.18632/oncotarget.19065.CrossRefPubMed

69.

Barcus, C. E., O'Leary, K. A., Brockman, J. L., Rugowski, D. E., Liu, Y., Garcia, N., et al. (2017). Elevated collagen-I augments tumor progressive signals, intravasation and metastasis of prolactin-induced estrogen receptor alpha positive mammary tumor cells. Breast Cancer Research, 19(1), 9. https://doi.org/10.1186/s13058-017-0801-1.CrossRefPubMedPubMedCentral

70.

Conklin, M. W., Eickhoff, J. C., Riching, K. M., Pehlke, C. A., Eliceiri, K. W., Provenzano, P. P., et al. (2011). Aligned collagen is a prognostic signature for survival in human breast carcinoma. The American Journal of Pathology, 178(3), 1221–1232. https://doi.org/10.1016/j.ajpath.2010.11.076.CrossRefPubMedPubMedCentral

71.

Morris, B. A., Burkel, B., Ponik, S. M., Fan, J., Condeelis, J. S., Aguirre-Ghiso, J. A., et al. (2016). Collagen matrix density drives the metabolic shift in breast cancer cells. EBioMedicine, 13, 146–156. https://doi.org/10.1016/j.ebiom.2016.10.012.CrossRefPubMedPubMedCentral

72.

Xiong, G., Deng, L., Zhu, J., Rychahou, P. G., & Xu, R. (2014). Prolyl-4-hydroxylase alpha subunit 2 promotes breast cancer progression and metastasis by regulating collagen deposition. BMC Cancer, 14, 1. https://doi.org/10.1186/1471-2407-14-1.CrossRefPubMedPubMedCentral

73.

Karousou, E., D'Angelo, M. L., Kouvidi, K., Vigetti, D., Viola, M., Nikitovic, D., et al. (2014). Collagen VI and hyaluronan: the common role in breast cancer. BioMed Research International, 2014, 606458. https://doi.org/10.1155/2014/606458.CrossRefPubMedPubMedCentral

74.

Castro-Sanchez, L., Soto-Guzman, A., Navarro-Tito, N., Martinez-Orozco, R., & Salazar, E. P. (2010). Native type IV collagen induces cell migration through a CD9 and DDR1-dependent pathway in MDA-MB-231 breast cancer cells. European Journal of Cell Biology, 89(11), 843–852. https://doi.org/10.1016/j.ejcb.2010.07.004.CrossRefPubMed

75.

Mazouni, C., Arun, B., Andre, F., Ayers, M., Krishnamurthy, S., Wang, B., et al. (2008). Collagen IV levels are elevated in the serum of patients with primary breast cancer compared to healthy volunteers. British Journal of Cancer, 99(1), 68–71. https://doi.org/10.1038/sj.bjc.6604443.CrossRefPubMedPubMedCentral

76.

Brodsky, A. S., Xiong, J., Yang, D., Schorl, C., Fenton, M. A., Graves, T. A., et al. (2016). Identification of stromal ColXalpha1 and tumor-infiltrating lymphocytes as putative predictive markers of neoadjuvant therapy in estrogen receptor-positive/HER2-positive breast cancer. BMC Cancer, 16, 274. https://doi.org/10.1186/s12885-016-2302-5.CrossRefPubMedPubMedCentral

77.

Wang, J. P., & Hielscher, A. (2017). Fibronectin: how its aberrant expression in tumors may improve therapeutic targeting. Journal of Cancer, 8(4), 674–682. https://doi.org/10.7150/jca.16901.CrossRefPubMedPubMedCentral

78.

Insua-Rodriguez, J., & Oskarsson, T. (2016). The extracellular matrix in breast cancer. Advanced Drug Delivery Reviews, 97, 41–55. https://doi.org/10.1016/j.addr.2015.12.017.CrossRefPubMed

79.

Multhaupt, H. A., Leitinger, B., Gullberg, D., & Couchman, J. R. (2016). Extracellular matrix component signaling in cancer. Advanced Drug Delivery Reviews, 97, 28–40. https://doi.org/10.1016/j.addr.2015.10.013.CrossRefPubMed

80.

Rybak, J. N., Roesli, C., Kaspar, M., Villa, A., & Neri, D. (2007). The extra-domain A of fibronectin is a vascular marker of solid tumors and metastases. Cancer Research, 67(22), 10948–10957. https://doi.org/10.1158/0008-5472.can-07-1436.CrossRefPubMed

81.

Ignotz, R. A., & Massague, J. (1986). Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. The Journal of Biological Chemistry, 261(9), 4337–4345.PubMed

82.

Mulsow, J. J., Watson, R. W., Fitzpatrick, J. M., & O'Connell, P. R. (2005). Transforming growth factor-beta promotes pro-fibrotic behavior by serosal fibroblasts via PKC and ERK1/2 mitogen activated protein kinase cell signaling. Annals of Surgery, 242(6), 880–887 discussion 887-889.CrossRefPubMedPubMedCentral

83.

Czaja, M. J., Weiner, F. R., Eghbali, M., Giambrone, M. A., Eghbali, M., & Zern, M. A. (1987). Differential effects of gamma-interferon on collagen and fibronectin gene expression. The Journal of Biological Chemistry, 262(27), 13348–13351.PubMed

84.

Erdogan, B., Ao, M., White, L. M., Means, A. L., Brewer, B. M., Yang, L., et al. (2017). Cancer-associated fibroblasts promote directional cancer cell migration by aligning fibronectin. The Journal of Cell Biology, 216(11), 3799–3816. https://doi.org/10.1083/jcb.201704053.CrossRefPubMedPubMedCentral

85.

Yao, E. S., Zhang, H., Chen, Y. Y., Lee, B., Chew, K., Moore, D., et al. (2007). Increased beta1 integrin is associated with decreased survival in invasive breast cancer. Cancer Research, 67(2), 659–664. https://doi.org/10.1158/0008-5472.can-06-2768.CrossRefPubMed

86.

Li, C. L., Yang, D., Cao, X., Wang, F., Hong, D. Y., Wang, J., et al. (2017). Fibronectin induces epithelial-mesenchymal transition in human breast cancer MCF-7 cells via activation of calpain. Oncology Letters, 13(5), 3889–3895. https://doi.org/10.3892/ol.2017.5896.CrossRefPubMedPubMedCentral

87.

Balanis, N., Wendt, M. K., Schiemann, B. J., Wang, Z., Schiemann, W. P., & Carlin, C. R. (2013). Epithelial to mesenchymal transition promotes breast cancer progression via a fibronectin-dependent STAT3 signaling pathway. The Journal of Biological Chemistry, 288(25), 17954–17967. https://doi.org/10.1074/jbc.M113.475277.CrossRefPubMedPubMedCentral

88.

Hong, H., Zhou, T., Fang, S., Jia, M., Xu, Z., Dai, Z., et al. (2014). Pigment epithelium-derived factor (PEDF) inhibits breast cancer metastasis by down-regulating fibronectin. Breast Cancer Research and Treatment, 148(1), 61–72. https://doi.org/10.1007/s10549-014-3154-9.CrossRefPubMed

89.

He, Z. H., Lei, Z., Zhen, Y., Gong, W., Huang, B., Yuan, Y., et al. (2014). Adeno-associated virus-mediated expression of recombinant CBD-HepII polypeptide of human fibronectin inhibits metastasis of breast cancer. Breast Cancer Research and Treatment, 143(1), 33–45. https://doi.org/10.1007/s10549-013-2783-8.CrossRefPubMed

90.

Park, C. C., Zhang, H., Pallavicini, M., Gray, J. W., Baehner, F., Park, C. J., et al. (2006). Beta1 integrin inhibitory antibody induces apoptosis of breast cancer cells, inhibits growth, and distinguishes malignant from normal phenotype in three dimensional cultures and in vivo. Cancer Research, 66(3), 1526–1535. https://doi.org/10.1158/0008-5472.can-05-3071.CrossRefPubMedPubMedCentral

91.

Sampayo, R. G., Toscani, A. M., Rubashkin, M. G., Thi, K., Masullo, L. A., Violi, I. L., et al. (2018). Fibronectin rescues estrogen receptor alpha from lysosomal degradation in breast cancer cells. The Journal of Cell Biology, 217(8), 2777–2798. https://doi.org/10.1083/jcb.201703037.CrossRefPubMedPubMedCentral

92.

Tucker, R. P., & Chiquet-Ehrismann, R. (2009). The regulation of tenascin expression by tissue microenvironments. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1793(5), 888–892. https://doi.org/10.1016/j.bbamcr.2008.12.012.CrossRef

93.

Hancox, R. A., Allen, M. D., Holliday, D. L., Edwards, D. R., Pennington, C. J., Guttery, D. S., et al. (2009). Tumour-associated tenascin-C isoforms promote breast cancer cell invasion and growth by matrix metalloproteinase-dependent and independent mechanisms. Breast Cancer Research, 11(2), R24. https://doi.org/10.1186/bcr2251.CrossRefPubMedPubMedCentral

94.

Yang, Z., Ni, W., Cui, C., Fang, L., & Xuan, Y. (2017). Tenascin C is a prognostic determinant and potential cancer-associated fibroblasts marker for breast ductal carcinoma. Experimental and Molecular Pathology, 102(2), 262–267. https://doi.org/10.1016/j.yexmp.2017.02.012.CrossRefPubMed

95.

Adams, M., Jones, J. L., Walker, R. A., Pringle, J. H., & Bell, S. C. (2002). Changes in tenascin-C isoform expression in invasive and preinvasive breast disease. Cancer Research, 62(11), 3289–3297.PubMed

96.

Oskarsson, T., Acharyya, S., Zhang, X. H. F., Vanharanta, S., Tavazoie, S. F., Morris, P. G., et al. (2011). Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. [Article]. Nature Medicine, 17, 867. https://doi.org/10.1038/nm.2379.CrossRefPubMedPubMedCentral

97.

Degen, M., Brellier, F., Schenk, S., Driscoll, R., Zaman, K., Stupp, R., et al. (2008). Tenascin-W, a new marker of cancer stroma, is elevated in sera of colon and breast cancer patients. International Journal of Cancer, 122(11), 2454–2461. https://doi.org/10.1002/ijc.23417.CrossRefPubMed

98.

Degen, M., Brellier, F., Kain, R., Ruiz, C., Terracciano, L., Orend, G., et al. (2007). Tenascin-W is a novel marker for activated tumor stroma in low-grade human breast cancer and influences cell behavior. Cancer Research, 67(19), 9169–9179. https://doi.org/10.1158/0008-5472.can-07-0666.CrossRefPubMed

99.

Brellier, F., Martina, E., Degen, M., Heuze-Vourc'h, N., Petit, A., Kryza, T., et al. (2012). Tenascin-W is a better cancer biomarker than tenascin-C for most human solid tumors. BMC Clinical Pathology, 12, 14. https://doi.org/10.1186/1472-6890-12-14.CrossRefPubMedPubMedCentral

100.

Chiovaro, F., Martina, E., Bottos, A., Scherberich, A., Hynes, N. E., & Chiquet-Ehrismann, R. (2015). Transcriptional regulation of tenascin-W by TGF-beta signaling in the bone metastatic niche of breast cancer cells. International Journal of Cancer, 137(8), 1842–1854. https://doi.org/10.1002/ijc.29565.CrossRefPubMedPubMedCentral

101.

Baker, A. M., Bird, D., Lang, G., Cox, T. R., & Erler, J. T. (2013). Lysyl oxidase enzymatic function increases stiffness to drive colorectal cancer progression through FAK. Oncogene, 32(14), 1863–1868. https://doi.org/10.1038/onc.2012.202.CrossRefPubMed

102.

Provenzano, P. P., Cuevas, C., Chang, A. E., Goel, V. K., Von Hoff, D. D., & Hingorani, S. R. (2012). Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell, 21(3), 418–429. https://doi.org/10.1016/j.ccr.2012.01.007.CrossRefPubMedPubMedCentral

103.

Provenzano, P. P., Eliceiri, K. W., Campbell, J. M., Inman, D. R., White, J. G., & Keely, P. J. (2006). Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Medicine, 4(1), 38. https://doi.org/10.1186/1741-7015-4-38.CrossRefPubMedPubMedCentral

104.

Levental, K. R., Yu, H., Kass, L., Lakins, J. N., Egeblad, M., Erler, J. T., et al. (2009). Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell, 139(5), 891–906. https://doi.org/10.1016/j.cell.2009.10.027.CrossRefPubMedPubMedCentral

105.

Wells, R. G. (2008). The role of matrix stiffness in regulating cell behavior. Hepatology, 47(4), 1394–1400. https://doi.org/10.1002/hep.22193.CrossRefPubMed

106.

Mouw, J. K., Yui, Y., Damiano, L., Bainer, R. O., Lakins, J. N., Acerbi, I., et al. (2014). Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression. Nature Medicine, 20(4), 360–367. https://doi.org/10.1038/nm.3497.CrossRefPubMedPubMedCentral

107.

Pickup, M. W., Laklai, H., Acerbi, I., Owens, P., Gorska, A. E., Chytil, A., et al. (2013). Stromally derived lysyl oxidase promotes metastasis of transforming growth factor-beta-deficient mouse mammary carcinomas. Cancer Research, 73(17), 5336–5346. https://doi.org/10.1158/0008-5472.can-13-0012.CrossRefPubMedPubMedCentral

108.

Erler, J. T., Bennewith, K. L., Nicolau, M., Dornhofer, N., Kong, C., Le, Q. T., et al. (2006). Lysyl oxidase is essential for hypoxia-induced metastasis. Nature, 440(7088), 1222–1226. https://doi.org/10.1038/nature04695.CrossRefPubMed

109.

Tang, X., Hou, Y., Yang, G., Wang, X., Tang, S., Du, Y. E., et al. (2016). Stromal miR-200s contribute to breast cancer cell invasion through CAF activation and ECM remodeling. Cell Death and Differentiation, 23(1), 132–145. https://doi.org/10.1038/cdd.2015.78.CrossRefPubMed

110.

El-Mohri, H., Wu, Y., Mohanty, S., & Ghosh, G. (2017). Impact of matrix stiffness on fibroblast function. Materials Science & Engineering. C, Materials for Biological Applications, 74, 146–151. https://doi.org/10.1016/j.msec.2017.02.001.CrossRef

111.

Asano, S., Ito, S., Takahashi, K., Furuya, K., Kondo, M., Sokabe, M., et al. (2017). Matrix stiffness regulates migration of human lung fibroblasts. Physiological Reports, 5(9). https://doi.org/10.14814/phy2.13281.

112.

Basset, P., Bellocq, J. P., Wolf, C., Stoll, I., Hutin, P., Limacher, J. M., et al. (1990). A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature, 348(6303), 699–704. https://doi.org/10.1038/348699a0.CrossRefPubMed

113.

Têtu, B., Brisson, J., Wang, C. S., Lapointe, H., Beaudry, G., Blanchette, C., et al. (2006). The influence of MMP-14, TIMP-2 and MMP-2 expression on breast cancer prognosis. [journal article]. Breast Cancer Research, 8(3), R28. https://doi.org/10.1186/bcr1503.CrossRefPubMedPubMedCentral

114.

Radisky, E. S., & Radisky, D. C. (2015). Matrix metalloproteinases as breast cancer drivers and therapeutic targets. Frontiers in Bioscience (Landmark edition), 20, 1144–1163.CrossRef

115.

Stuelten, C. H., DaCosta Byfield, S., Arany, P. R., Karpova, T. S., Stetler-Stevenson, W. G., & Roberts, A. B. (2005). Breast cancer cells induce stromal fibroblasts to express MMP-9 via secretion of TNF-alpha and TGF-beta. Journal of Cell Science, 118(Pt 10), 2143–2153. https://doi.org/10.1242/jcs.02334.CrossRefPubMed

116.

Saad, S., Gottlieb, D. J., Bradstock, K. F., Overall, C. M., & Bendall, L. J. (2002). Cancer cell-associated fibronectin induces release of matrix metalloproteinase-2 from normal fibroblasts. Cancer Research, 62, 283–289.PubMed

117.

Lochter, A., Galosy, S., Muschler, J., Freedman, N., Werb, Z., & Bissell, M. J. (1997). Matrix metalloproteinase stromelysin-1 triggers a cascade of molecular alterations that leads to stable epithelial-to-mesenchymal conversion and a premalignant phenotype in mammary epithelial cells. The Journal of Cell Biology, 139(7), 1861–1872.CrossRefPubMedPubMedCentral

118.

Xu, H., Li, M., Zhou, Y., Wang, F., Li, X., Wang, L., et al. (2016). S100A4 participates in epithelial-mesenchymal transition in breast cancer via targeting MMP2. Tumour Biology, 37(3), 2925–2932. https://doi.org/10.1007/s13277-015-3709-3.CrossRefPubMed

119.

Liss, M., Sreedhar, N., Keshgegian, A., Sauter, G., Chernick, M. R., Prendergast, G. C., et al. (2009). Tissue inhibitor of metalloproteinase-4 is elevated in early-stage breast cancers with accelerated progression and poor clinical course. The American Journal of Pathology, 175(3), 940–946. https://doi.org/10.2353/ajpath.2009.081094.CrossRefPubMedPubMedCentral

120.

Gong, Y., Scott, E., Lu, R., Xu, Y., Oh, W. K., & Yu, Q. (2013). TIMP-1 promotes accumulation of cancer associated fibroblasts and cancer progression. PLoS One, 8(10), e77366. https://doi.org/10.1371/journal.pone.0077366.CrossRefPubMedPubMedCentral

121.

Song, T., Dou, C., Jia, Y., Tu, K., & Zheng, X. (2015). TIMP-1 activated carcinoma-associated fibroblasts inhibit tumor apoptosis by activating SDF1/CXCR4 signaling in hepatocellular carcinoma. Oncotarget, 6(14), 12061–12079. https://doi.org/10.18632/oncotarget.3616.CrossRefPubMedPubMedCentral

122.

Dang, T. T., Prechtl, A. M., & Pearson, G. W. (2011). Breast cancer subtype-specific interactions with the microenvironment dictate mechanisms of invasion. Cancer Research, 71(21), 6857–6866. https://doi.org/10.1158/0008-5472.can-11-1818.CrossRefPubMedPubMedCentral

123.

Hu, M., Yao, J., Carroll, D. K., Weremowicz, S., Chen, H., Carrasco, D., et al. (2008). Regulation of in situ to invasive breast carcinoma transition. Cancer Cell, 13(5), 394–406. https://doi.org/10.1016/j.ccr.2008.03.007.CrossRefPubMedPubMedCentral

124.

Osuala, K. O., Sameni, M., Shah, S., Aggarwal, N., Simonait, M. L., Franco, O. E., et al. (2015). Il-6 signaling between ductal carcinoma in situ cells and carcinoma-associated fibroblasts mediates tumor cell growth and migration. BMC Cancer, 15, 584. https://doi.org/10.1186/s12885-015-1576-3.CrossRefPubMedPubMedCentral

125.

Yu, Y., Xiao, C. H., Tan, L. D., Wang, Q. S., Li, X. Q., & Feng, Y. M. (2014). Cancer-associated fibroblasts induce epithelial-mesenchymal transition of breast cancer cells through paracrine TGF-beta signalling. British Journal of Cancer, 110(3), 724–732. https://doi.org/10.1038/bjc.2013.768.CrossRefPubMed

126.

Takai, K., Le, A., Weaver, V. M., & Werb, Z. (2016). Targeting the cancer-associated fibroblasts as a treatment in triple-negative breast cancer. Oncotarget, 7(50), 82889–82901. https://doi.org/10.18632/oncotarget.12658.CrossRefPubMedPubMedCentral

127.

Bellomo, C., Caja, L., & Moustakas, A. (2016). Transforming growth factor β as regulator of cancer stemness and metastasis. British Journal of Cancer, 115(7), 761–769. https://doi.org/10.1038/bjc.2016.255.CrossRefPubMedPubMedCentral

128.

Dvorak, K. M., Pettee, K. M., Rubinic-Minotti, K., Su, R., Nestor-Kalinoski, A., & Eisenmann, K. M. (2018). Carcinoma associated fibroblasts (CAFs) promote breast cancer motility by suppressing mammalian Diaphanous-related formin-2 (mDia2). PLoS One, 13(3), e0195278. https://doi.org/10.1371/journal.pone.0195278.CrossRefPubMedPubMedCentral

129.

Ahirwar, D. K., Nasser, M. W., Ouseph, M. M., Elbaz, M., Cuitino, M. C., Kladney, R. D., et al. (2018). Fibroblast-derived CXCL12 promotes breast cancer metastasis by facilitating tumor cell intravasation. Oncogene. https://doi.org/10.1038/s41388-018-0263-7.

130.

O'Connell, J. T., Sugimoto, H., Cooke, V. G., MacDonald, B. A., Mehta, A. I., LeBleu, V. S., et al. (2011). VEGF-A and tenascin-C produced by S100A4+ stromal cells are important for metastatic colonization. Proceedings of the National Academy of Sciences of the United States of America, 108(38), 16002–16007. https://doi.org/10.1073/pnas.1109493108.CrossRefPubMedPubMedCentral

131.

Studebaker, A. W., Storci, G., Werbeck, J. L., Sansone, P., Sasser, A. K., Tavolari, S., et al. (2008). Fibroblasts isolated from common sites of breast cancer metastasis enhance cancer cell growth rates and invasiveness in an interleukin-6-dependent manner. Cancer Research, 68(21), 9087–9095. https://doi.org/10.1158/0008-5472.can-08-0400.CrossRefPubMed

132.

Xu, K., Tian, X., Oh, S. Y., Movassaghi, M., Naber, S. P., Kuperwasser, C., et al. (2016). The fibroblast Tiam1-osteopontin pathway modulates breast cancer invasion and metastasis. Breast Cancer Research, 18(1), 14. https://doi.org/10.1186/s13058-016-0674-8.CrossRefPubMedPubMedCentral

133.

Lowry, M. C., Gallagher, W. M., & O'Driscoll, L. (2015). The role of exosomes in breast cancer. Clinical Chemistry, 61(12), 1457–1465. https://doi.org/10.1373/clinchem.2015.240028.CrossRefPubMed

134.

Chen, Y., Zeng, C., Zhan, Y., Wang, H., Jiang, X., & Li, W. (2017). Aberrant low expression of p85α in stromal fibroblasts promotes breast cancer cell metastasis through exosome-mediated paracrine Wnt10b. [original article]. Oncogene, 36, 4692. https://doi.org/10.1038/onc.2017.100.CrossRefPubMedPubMedCentral

135.

Luga, V., Zhang, L., Viloria-Petit, A. M., Ogunjimi, A. A., Inanlou, M. R., Chiu, E., et al. (2012). Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell, 151(7), 1542–1556. https://doi.org/10.1016/j.cell.2012.11.024.CrossRefPubMed

136.

Shimoda, M., Principe, S., Jackson, H. W., Luga, V., Fang, H., Molyneux, S. D., et al. (2014). Loss of the Timp gene family is sufficient for the acquisition of the CAF-like cell state. Nature Cell Biology, 16(9), 889–901. https://doi.org/10.1038/ncb3021.CrossRefPubMed

137.

Nabet, B. Y., Qiu, Y., Shabason, J. E., Wu, T. J., Yoon, T., Kim, B. C., et al. (2017). Exosome RNA unshielding couples stromal activation to pattern recognition receptor signaling in cancer. Cell, 170(2), 352–366.e313. https://doi.org/10.1016/j.cell.2017.06.031.CrossRefPubMedPubMedCentral

138.

Choi, Y. P., Lee, J. H., Gao, M. Q., Kim, B. G., Kang, S., Kim, S. H., et al. (2014). Cancer-associated fibroblast promote transmigration through endothelial brain cells in three-dimensional in vitro models. International Journal of Cancer, 135(9), 2024–2033. https://doi.org/10.1002/ijc.28848.CrossRefPubMed

139.

Gaggioli, C., Hooper, S., Hidalgo-Carcedo, C., Grosse, R., Marshall, J. F., Harrington, K., et al. (2007). Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nature Cell Biology, 9(12), 1392–1400. https://doi.org/10.1038/ncb1658.CrossRefPubMed

140.

Yang, N., Mosher, R., Seo, S., Beebe, D., & Friedl, A. (2011). Syndecan-1 in breast cancer stroma fibroblasts regulates extracellular matrix fiber organization and carcinoma cell motility. The American Journal of Pathology, 178(1), 325–335. https://doi.org/10.1016/j.ajpath.2010.11.039.CrossRefPubMedPubMedCentral

141.

Chute, C., Yang, X., Meyer, K., Yang, N., O'Neil, K., Kasza, I., et al. (2018). Syndecan-1 induction in lung microenvironment supports the establishment of breast tumor metastases. Breast Cancer Research, 20(1), 66. https://doi.org/10.1186/s13058-018-0995-x.CrossRefPubMedPubMedCentral

142.

Corsa, C. A., Brenot, A., Grither, W. R., Van Hove, S., Loza, A. J., Zhang, K., et al. (2016). The action of Discoidin domain receptor 2 in basal tumor cells and stromal cancer-associated fibroblasts is critical for breast cancer metastasis. Cell Reports, 15(11), 2510–2523. https://doi.org/10.1016/j.celrep.2016.05.033.CrossRefPubMed

143.

Farmaki, E., Chatzistamou, I., Kaza, V., & Kiaris, H. (2016). A CCL8 gradient drives breast cancer cell dissemination. Oncogene, 35(49), 6309–6318. https://doi.org/10.1038/onc.2016.161.CrossRefPubMedPubMedCentral

144.

Wang, K., Wu, F., Seo, B. R., Fischbach, C., Chen, W., Hsu, L., et al. (2017). Breast cancer cells alter the dynamics of stromal fibronectin-collagen interactions. Matrix Biology, 60-61, 86–95. https://doi.org/10.1016/j.matbio.2016.08.001.CrossRefPubMed

145.

Dvorak, H. F. (1986). Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. The New England Journal of Medicine, 315(26), 1650–1659. https://doi.org/10.1056/nejm198612253152606.CrossRefPubMed

146.

Hanahan, D., & Coussens, L. M. (2012). Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell, 21(3), 309–322. https://doi.org/10.1016/j.ccr.2012.02.022.CrossRefPubMed

147.

Neuzillet, C., Tijeras-Raballand, A., Cohen, R., Cros, J., Faivre, S., Raymond, E., et al. (2015). Targeting the TGFbeta pathway for cancer therapy. Pharmacology & Therapeutics, 147, 22–31. https://doi.org/10.1016/j.pharmthera.2014.11.001.CrossRef

148.

Ziani, L., Chouaib, S., & Thiery, J. (2018). Alteration of the antitumor immune response by cancer-associated fibroblasts. Frontiers in Immunology, 9, 414. https://doi.org/10.3389/fimmu.2018.00414.CrossRefPubMedPubMedCentral

149.

Kinoshita, T., Ishii, G., Hiraoka, N., Hirayama, S., Yamauchi, C., Aokage, K., et al. (2013). Forkhead box P3 regulatory T cells coexisting with cancer associated fibroblasts are correlated with a poor outcome in lung adenocarcinoma. Cancer Science, 104(4), 409–415. https://doi.org/10.1111/cas.12099.CrossRefPubMedPubMedCentral

150.

Li, T., Yi, S., Liu, W., Jia, C., Wang, G., Hua, X., et al. (2013). Colorectal carcinoma-derived fibroblasts modulate natural killer cell phenotype and antitumor cytotoxicity. Medical Oncology, 30(3), 663. https://doi.org/10.1007/s12032-013-0663-z.CrossRefPubMed

151.

Shen, C. C., Kang, Y. H., Zhao, M., He, Y., Cui, D. D., Fu, Y. Y., et al. (2014). WNT16B from ovarian fibroblasts induces differentiation of regulatory T cells through beta-catenin signal in dendritic cells. International Journal of Molecular Sciences, 15(7), 12928–12939. https://doi.org/10.3390/ijms150712928.CrossRefPubMedPubMedCentral

152.

Takahashi, H., Sakakura, K., Kudo, T., Toyoda, M., Kaira, K., Oyama, T., et al. (2017). Cancer-associated fibroblasts promote an immunosuppressive microenvironment through the induction and accumulation of protumoral macrophages. Oncotarget, 8(5), 8633–8647. https://doi.org/10.18632/oncotarget.14374.CrossRefPubMed

153.

Fu, Z., Zuo, Y., Li, D., Xu, W., Li, D., Chen, H., et al. (2013). The crosstalk: tumor-infiltrating lymphocytes rich in regulatory T cells suppressed cancer-associated fibroblasts. Acta Oncologica, 52(8), 1760–1770. https://doi.org/10.3109/0284186X.2012.760847.CrossRefPubMed

154.

Allaoui, R., Bergenfelz, C., Mohlin, S., Hagerling, C., Salari, K., Werb, Z., et al. (2016). Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers. Nature Communications, 7, 13050. https://doi.org/10.1038/ncomms13050.CrossRefPubMedPubMedCentral

155.

Silzle, T., Kreutz, M., Dobler, M. A., Brockhoff, G., Knuechel, R., & Kunz-Schughart, L. A. (2003). Tumor-associated fibroblasts recruit blood monocytes into tumor tissue. European Journal of Immunology, 33(5), 1311–1320. https://doi.org/10.1002/eji.200323057.CrossRefPubMed

156.

Qian, B. Z., Li, J., Zhang, H., Kitamura, T., Zhang, J., Campion, L. R., et al. (2011). CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature, 475(7355), 222–225. https://doi.org/10.1038/nature10138.CrossRefPubMedPubMedCentral

157.

Liao, D., Luo, Y., Markowitz, D., Xiang, R., & Reisfeld, R. A. (2009). Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model. PLoS One, 4(11), e7965. https://doi.org/10.1371/journal.pone.0007965.CrossRefPubMedPubMedCentral

158.

Li, A., Chen, P., Leng, Y., & Kang, J. (2018). Histone deacetylase 6 regulates the immunosuppressive properties of cancer-associated fibroblasts in breast cancer through the STAT3-COX2-dependent pathway. Oncogene. https://doi.org/10.1038/s41388-018-0379-9.

159.

Cohen, N., Shani, O., Raz, Y., Sharon, Y., Hoffman, D., Abramovitz, L., et al. (2017). Fibroblasts drive an immunosuppressive and growth-promoting microenvironment in breast cancer via secretion of Chitinase 3-like 1. Oncogene, 36(31), 4457–4468. https://doi.org/10.1038/onc.2017.65.CrossRefPubMedPubMedCentral

160.

Costa, A., Kieffer, Y., Scholer-Dahirel, A., Pelon, F., Bourachot, B., Cardon, M., et al. (2018). Fibroblast heterogeneity and immunosuppressive environment in human breast cancer. Cancer Cell, 33(3), 463–479.e410. https://doi.org/10.1016/j.ccell.2018.01.011.CrossRefPubMed

161.

Panagopoulos, V., Leach, D. A., Zinonos, I., Ponomarev, V., Licari, G., Liapis, V., et al. (2017). Inflammatory peroxidases promote breast cancer progression in mice via regulation of the tumour microenvironment. International Journal of Oncology, 50(4), 1191–1200. https://doi.org/10.3892/ijo.2017.3883.CrossRefPubMed

162.

Lu, P., Weaver, V. M., & Werb, Z. (2012). The extracellular matrix: a dynamic niche in cancer progression. The Journal of Cell Biology, 196(4), 395–406. https://doi.org/10.1083/jcb.201102147.CrossRefPubMedPubMedCentral

163.

Bae, Y. K., Kim, A., Kim, M. K., Choi, J. E., Kang, S. H., & Lee, S. J. (2013). Fibronectin expression in carcinoma cells correlates with tumor aggressiveness and poor clinical outcome in patients with invasive breast cancer. Human Pathology, 44(10), 2028–2037. https://doi.org/10.1016/j.humpath.2013.03.006.CrossRefPubMed

164.

Fernandez-Garcia, B., Eiro, N., Marin, L., Gonzalez-Reyes, S., Gonzalez, L. O., Lamelas, M. L., et al. (2014). Expression and prognostic significance of fibronectin and matrix metalloproteases in breast cancer metastasis. Histopathology, 64(4), 512–522. https://doi.org/10.1111/his.12300.CrossRefPubMed

165.

Acerbi, I., Cassereau, L., Dean, I., Shi, Q., Au, A., Park, C., et al. (2015). Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration. Integrative Biology: Quantitative Biosciences from Nano to Macro, 7(10), 1120–1134. https://doi.org/10.1039/c5ib00040h.CrossRef

166.

Jachetti, E., Caputo, S., Mazzoleni, S., Brambillasca, C. S., Parigi, S. M., Grioni, M., et al. (2015). Tenascin-C protects cancer stem-like cells from immune surveillance by arresting T-cell activation. Cancer Research, 75(10), 2095–2108. https://doi.org/10.1158/0008-5472.can-14-2346.CrossRefPubMed

167.

Huang, J. Y., Cheng, Y. J., Lin, Y. P., Lin, H. C., Su, C. C., Juliano, R., et al. (2010). Extracellular matrix of glioblastoma inhibits polarization and transmigration of T cells: the role of tenascin-C in immune suppression. Journal of Immunology, 185(3), 1450–1459. https://doi.org/10.4049/jimmunol.0901352.CrossRef

168.

Tsunoda, T., Inada, H., Kalembeyi, I., Imanaka-Yoshida, K., Sakakibara, M., Okada, R., et al. (2003). Involvement of large tenascin-C splice variants in breast cancer progression. The American Journal of Pathology, 162(6), 1857–1867. https://doi.org/10.1016/s0002-9440(10)64320-9.CrossRefPubMedPubMedCentral

169.

Kelsh, R., You, R., Horzempa, C., Zheng, M., & McKeown-Longo, P. J. (2014). Regulation of the innate immune response by fibronectin: synergism between the III-1 and EDA domains. PLoS One, 9(7), e102974. https://doi.org/10.1371/journal.pone.0102974.CrossRefPubMedPubMedCentral

170.

Rossnagl, S., Altrock, E., Sens, C., Kraft, S., Rau, K., Milsom, M. D., et al. (2016). EDA-fibronectin originating from osteoblasts inhibits the immune response against cancer. PLoS Biology, 14(9), e1002562. https://doi.org/10.1371/journal.pbio.1002562.CrossRefPubMedPubMedCentral

171.

Farmer, P., Bonnefoi, H., Anderle, P., Cameron, D., Wirapati, P., Becette, V., et al. (2009). A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nature Medicine, 15(1), 68–74. https://doi.org/10.1038/nm.1908.CrossRefPubMed

172.

Jia, D., Liu, Z., Deng, N., Tan, T. Z., Huang, R. Y., Taylor-Harding, B., et al. (2016). A COL11A1-correlated pan-cancer gene signature of activated fibroblasts for the prioritization of therapeutic targets. Cancer Letters, 382(2), 203–214. https://doi.org/10.1016/j.canlet.2016.09.001.CrossRefPubMedPubMedCentral

173.

Cukierman, E., & Bassi, D. E. (2012). The mesenchymal tumor microenvironment. Cell Adhesion & Migration, 6(3), 285–296. https://doi.org/10.4161/cam.20210.CrossRef

174.

Shain, K. H., & Dalton, W. S. (2001). Cell adhesion is a key determinant in de novo multidrug resistance (MDR): new targets for the prevention of acquired MDR. Molecular Cancer Therapeutics, 1(1), 69–78.PubMed

175.

Giussani, M., Merlino, G., Cappelletti, V., Tagliabue, E., & Daidone, M. G. (2015). Tumor-extracellular matrix interactions: identification of tools associated with breast cancer progression. Seminars in Cancer Biology, 35, 3–10. https://doi.org/10.1016/j.semcancer.2015.09.012.CrossRefPubMed

176.

Soon, P. S., Kim, E., Pon, C. K., Gill, A. J., Moore, K., Spillane, A. J., et al. (2013). Breast cancer-associated fibroblasts induce epithelial-to-mesenchymal transition in breast cancer cells. Endocrine-Related Cancer, 20(1), 1–12. https://doi.org/10.1530/erc-12-0227.CrossRefPubMed

177.

Gao, M. Q., Kim, B. G., Kang, S., Choi, Y. P., Park, H., Kang, K. S., et al. (2010). Stromal fibroblasts from the interface zone of human breast carcinomas induce an epithelial-mesenchymal transition-like state in breast cancer cells in vitro. Journal of Cell Science, 123(Pt 20), 3507–3514. https://doi.org/10.1242/jcs.072900.CrossRefPubMed

178.

Yuan, J., Liu, M., Yang, L., Tu, G., Zhu, Q., Chen, M., et al. (2015). Acquisition of epithelial-mesenchymal transition phenotype in the tamoxifen-resistant breast cancer cell: a new role for G protein-coupled estrogen receptor in mediating tamoxifen resistance through cancer-associated fibroblast-derived fibronectin and beta1-integrin signaling pathway in tumor cells. Breast Cancer Research, 17, 69. https://doi.org/10.1186/s13058-015-0579-y.CrossRefPubMedPubMedCentral

179.

Amornsupak, K., Insawang, T., Thuwajit, P., O-Charoenrat, P., Eccles, S. A., & Thuwajit, C. (2014). Cancer-associated fibroblasts induce high mobility group box 1 and contribute to resistance to doxorubicin in breast cancer cells. BMC Cancer, 14, 955. https://doi.org/10.1186/1471-2407-14-955.CrossRefPubMedPubMedCentral

180.

Huang, J., Ni, J., Liu, K., Yu, Y., Xie, M., Kang, R., et al. (2012). HMGB1 promotes drug resistance in osteosarcoma. Cancer Research, 72(1), 230–238. https://doi.org/10.1158/0008-5472.can-11-2001.CrossRefPubMed

181.

Boelens, M. C., Wu, T. J., Nabet, B. Y., Xu, B., Qiu, Y., Yoon, T., et al. (2014). Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways. Cell, 159(3), 499–513. https://doi.org/10.1016/j.cell.2014.09.051.CrossRefPubMedPubMedCentral

182.

Cui, Q., Wang, B., Li, K., Sun, H., Hai, T., Zhang, Y., et al. (2018). Upregulating MMP-1 in carcinoma-associated fibroblasts reduces the efficacy of Taxotere on breast cancer synergized by Collagen IV. Oncology Letters, 16(3), 3537–3544. https://doi.org/10.3892/ol.2018.9092.CrossRefPubMedPubMedCentral

183.

Landry, B. D., Leete, T., Richards, R., Cruz-Gordillo, P., Schwartz, H. R., Honeywell, M. E., et al. (2018). Tumor-stroma interactions differentially alter drug sensitivity based on the origin of stromal cells. Molecular Systems Biology, 14(8), e8322–10.15252/msb.20188322.CrossRefPubMedPubMedCentral

184.

Marusyk, A., Tabassum, D. P., Janiszewska, M., Place, A. E., Trinh, A., Rozhok, A. I., et al. (2016). Spatial proximity to fibroblasts impacts molecular features and therapeutic sensitivity of breast cancer cells influencing clinical outcomes. Cancer Research, 76(22), 6495–6506. https://doi.org/10.1158/0008-5472.can-16-1457.CrossRefPubMedPubMedCentral

185.

Senthebane, D. A., Rowe, A., Thomford, N. E., Shipanga, H., Munro, D., Al Mazeedi, M. A. M., et al. (2017). The role of tumor microenvironment in chemoresistance: to survive, keep your enemies closer. International Journal of Molecular Sciences, 18(7), 1586. https://doi.org/10.3390/ijms18071586.CrossRefPubMedCentral

186.

Lin, C. H., Pelissier, F. A., Zhang, H., Lakins, J., Weaver, V. M., Park, C., et al. (2015). Microenvironment rigidity modulates responses to the HER2 receptor tyrosine kinase inhibitor lapatinib via YAP and TAZ transcription factors. Molecular Biology of the Cell, 26(22), 3946–3953. https://doi.org/10.1091/mbc.E15-07-0456.CrossRefPubMedPubMedCentral

187.

Ozdemir, B. C., Pentcheva-Hoang, T., Carstens, J. L., Zheng, X., Wu, C. C., Simpson, T. R., et al. (2015). Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell, 28(6), 831–833. https://doi.org/10.1016/j.ccell.2015.11.002.CrossRefPubMed

188.

Duyverman, A. M. M. J., Steller, E. J. A., Fukumura, D., Jain, R. K., & Duda, D. G. (2012). Studying primary tumor-associated fibroblast involvement in cancer metastasis in mice. Nature Protocols, 7(4), 756–762. https://doi.org/10.1038/nprot.2012.031.CrossRefPubMedPubMedCentral

189.

Rhim, A. D., Oberstein, P. E., Thomas, D. H., Mirek, E. T., Palermo, C. F., Sastra, S. A., et al. (2014). Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell, 25(6), 735–747. https://doi.org/10.1016/j.ccr.2014.04.021.CrossRefPubMedPubMedCentral

190.

Yauch, R. L., Gould, S. E., Scales, S. J., Tang, T., Tian, H., Ahn, C. P., et al. (2008). A paracrine requirement for hedgehog signalling in cancer. Nature, 455(7211), 406–410. https://doi.org/10.1038/nature07275.CrossRefPubMed

191.

Olive, K. P., Jacobetz, M. A., Davidson, C. J., Gopinathan, A., McIntyre, D., Honess, D., et al. (2009). Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science, 324(5933), 1457–1461. https://doi.org/10.1126/science.1171362.CrossRefPubMedPubMedCentral

192.

Ko, A. H., LoConte, N., Tempero, M. A., Walker, E. J., Kate Kelley, R., Lewis, S., et al. (2016). A phase I study of FOLFIRINOX plus IPI-926, a hedgehog pathway inhibitor, for advanced pancreatic adenocarcinoma. Pancreas, 45(3), 370–375. https://doi.org/10.1097/mpa.0000000000000458.CrossRefPubMedPubMedCentral

193.

Fearon, D. T. (2014). The carcinoma-associated fibroblast expressing fibroblast activation protein and escape from immune surveillance. Cancer Immunology Research, 2(3), 187–193. https://doi.org/10.1158/2326-6066.cir-14-0002.CrossRefPubMed

194.

Kraman, M., Bambrough, P. J., Arnold, J. N., Roberts, E. W., Magiera, L., Jones, J. O., et al. (2010). Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science, 330(6005), 827–830. https://doi.org/10.1126/science.1195300.CrossRefPubMed

195.

Duperret, E. K., Trautz, A., Ammons, D., Perales-Puchalt, A., Wise, M. C., Yan, J., et al. (2018). Alteration of the tumor stroma using a consensus DNA vaccine targeting fibroblast activation protein (FAP) synergizes with antitumor vaccine therapy in mice. Clinical Cancer Research, 24(5), 1190–1201. https://doi.org/10.1158/1078-0432.ccr-17-2033.CrossRefPubMed

196.

Gottschalk, S., Yu, F., Ji, M., Kakarla, S., & Song, X. T. (2013). A vaccine that co-targets tumor cells and cancer associated fibroblasts results in enhanced antitumor activity by inducing antigen spreading. PLoS One, 8(12), e82658. https://doi.org/10.1371/journal.pone.0082658.CrossRefPubMedPubMedCentral

197.

Loeffler, M., Kruger, J. A., Niethammer, A. G., & Reisfeld, R. A. (2006). Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake. The Journal of Clinical Investigation, 116(7), 1955–1962. https://doi.org/10.1172/jci26532.CrossRefPubMedPubMedCentral

198.

Meng, M., Wang, W., Yan, J., Tan, J., Liao, L., Shi, J., et al. (2016). Immunization of stromal cell targeting fibroblast activation protein providing immunotherapy to breast cancer mouse model. Tumour Biology, 37(8), 10317–10327. https://doi.org/10.1007/s13277-016-4825-4.CrossRefPubMed

199.

Ostermann, E., Garin-Chesa, P., Heider, K. H., Kalat, M., Lamche, H., Puri, C., et al. (2008). Effective immunoconjugate therapy in cancer models targeting a serine protease of tumor fibroblasts. Clinical Cancer Research, 14(14), 4584–4592. https://doi.org/10.1158/1078-0432.ccr-07-5211.CrossRefPubMed

200.

Femel, J., Huijbers, E. J., Saupe, F., Cedervall, J., Zhang, L., Roswall, P., et al. (2014). Therapeutic vaccination against fibronectin ED-A attenuates progression of metastatic breast cancer. Oncotarget, 5(23), 12418–12427. https://doi.org/10.18632/oncotarget.2628.CrossRefPubMedPubMedCentral

201.

Park, C. Y., Min, K. N., Son, J. Y., Park, S. Y., Nam, J. S., Kim, D. K., et al. (2014). An novel inhibitor of TGF-beta type I receptor, IN-1130, blocks breast cancer lung metastasis through inhibition of epithelial-mesenchymal transition. Cancer Letters, 351(1), 72–80. https://doi.org/10.1016/j.canlet.2014.05.006.CrossRefPubMed

202.

Fang, Y., Chen, Y., Yu, L., Zheng, C., Qi, Y., Li, Z., et al. (2013). Inhibition of breast cancer metastases by a novel inhibitor of TGFbeta receptor 1. Journal of the National Cancer Institute, 105(1), 47–58. https://doi.org/10.1093/jnci/djs485.CrossRefPubMed

203.

Ehata, S., Hanyu, A., Fujime, M., Katsuno, Y., Fukunaga, E., Goto, K., et al. (2007). Ki26894, a novel transforming growth factor-beta type I receptor kinase inhibitor, inhibits in vitro invasion and in vivo bone metastasis of a human breast cancer cell line. Cancer Science, 98(1), 127–133. https://doi.org/10.1111/j.1349-7006.2006.00357.x.CrossRefPubMed

204.

Bandyopadhyay, A., Agyin, J. K., Wang, L., Tang, Y., Lei, X., Story, B. M., et al. (2006). Inhibition of pulmonary and skeletal metastasis by a transforming growth factor-β type I receptor kinase inhibitor. Cancer Research, 66(13), 6714–6721. https://doi.org/10.1158/0008-5472.can-05-3565.CrossRefPubMed

205.

Formenti, S. C., Lee, P., Adams, S., Goldberg, J. D., Li, X., Xie, M. W., et al. (2018). Focal irradiation and systemic TGFbeta blockade in metastatic breast cancer. Clinical Cancer Research, 24(11), 2493–2504. https://doi.org/10.1158/1078-0432.ccr-17-3322.CrossRefPubMedPubMedCentral

206.

Giaccone, G., Bazhenova, L. A., Nemunaitis, J., Tan, M., Juhasz, E., Ramlau, R., et al. (2015). A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer. European Journal of Cancer, 51(16), 2321–2329. https://doi.org/10.1016/j.ejca.2015.07.035.CrossRefPubMed

207.

Xiang, J., Hurchla, M. A., Fontana, F., Su, X., Amend, S. R., Esser, A. K., et al. (2015). CXCR4 protein epitope mimetic antagonist POL5551 disrupts metastasis and enhances chemotherapy effect in triple-negative breast cancer. Molecular Cancer Therapeutics, 14(11), 2473–2485. https://doi.org/10.1158/1535-7163.mct-15-0252.CrossRefPubMedPubMedCentral

208.

Peng, S. B., Zhang, X., Paul, D., Kays, L. M., Gough, W., Stewart, J., et al. (2015). Identification of LY2510924, a novel cyclic peptide CXCR4 antagonist that exhibits antitumor activities in solid tumor and breast cancer metastatic models. Molecular Cancer Therapeutics, 14(2), 480–490. https://doi.org/10.1158/1535-7163.mct-14-0850.CrossRefPubMed

209.

Ling, X., Spaeth, E., Chen, Y., Shi, Y., Zhang, W., Schober, W., et al. (2013). The CXCR4 antagonist AMD3465 regulates oncogenic signaling and invasiveness in vitro and prevents breast cancer growth and metastasis in vivo. PLoS One, 8(3), e58426. https://doi.org/10.1371/journal.pone.0058426.CrossRefPubMedPubMedCentral

210.

Galsky, M. D., Vogelzang, N. J., Conkling, P., Raddad, E., Polzer, J., Roberson, S., et al. (2014). A phase I trial of LY2510924, a CXCR4 peptide antagonist, in patients with advanced cancer. Clinical Cancer Research, 20(13), 3581–3588. https://doi.org/10.1158/1078-0432.ccr-13-2686.CrossRefPubMed

211.

Hainsworth, J. D., Reeves, J. A., Mace, J. R., Crane, E. J., Hamid, O., Stille, J. R., et al. (2016). A randomized, open-label phase 2 study of the CXCR4 inhibitor LY2510924 in combination with sunitinib versus sunitinib alone in patients with metastatic renal cell carcinoma (RCC). Targeted Oncology, 11(5), 643–653. https://doi.org/10.1007/s11523-016-0434-9.CrossRefPubMed

212.

Salgia, R., Stille, J. R., Weaver, R. W., McCleod, M., Hamid, O., Polzer, J., et al. (2017). A randomized phase II study of LY2510924 and carboplatin/etoposide versus carboplatin/etoposide in extensive-disease small cell lung cancer. Lung Cancer, 105, 7–13. https://doi.org/10.1016/j.lungcan.2016.12.020.CrossRefPubMed

213.

Loktev, A., Lindner, T., Mier, W., Debus, J., Altmann, A., Jager, D., et al. (2018). A tumor-imaging method targeting cancer-associated fibroblasts. Journal of Nuclear Medicine, 59(9), 1423–1429. https://doi.org/10.2967/jnumed.118.210435.CrossRefPubMedPubMedCentral

214.

Zhou, Z., Qutaish, M., Han, Z., Schur, R. M., Liu, Y., Wilson, D. L., et al. (2015). MRI detection of breast cancer micrometastases with a fibronectin-targeting contrast agent. Nature Communications, 6, 7984. https://doi.org/10.1038/ncomms8984.CrossRefPubMed

215.

Butsch, V., Borgel, F., Galla, F., Schwegmann, K., Hermann, S., Schafers, M., et al. (2018). Design, (radio)synthesis, and in vitro and in vivo evaluation of highly selective and potent matrix metalloproteinase 12 (MMP-12) inhibitors as radiotracers for positron emission tomography. Journal of Medicinal Chemistry, 61(9), 4115–4134. https://doi.org/10.1021/acs.jmedchem.8b00200.CrossRefPubMed

216.

Matusiak, N., Castelli, R., Tuin, A. W., Overkleeft, H. S., Wisastra, R., Dekker, F. J., et al. (2015). A dual inhibitor of matrix metalloproteinases and a disintegrin and metalloproteinases, [(1)(8)F]FB-ML5, as a molecular probe for non-invasive MMP/ADAM-targeted imaging. Bioorganic & Medicinal Chemistry, 23(1), 192–202. https://doi.org/10.1016/j.bmc.2014.11.013.CrossRef

217.

Matusiak, N., van Waarde, A., Bischoff, R., Oltenfreiter, R., van de Wiele, C., Dierckx, R. A., et al. (2013). Probes for non-invasive matrix metalloproteinase-targeted imaging with PET and SPECT. Current Pharmaceutical Design, 19(25), 4647–4672.CrossRefPubMed

218.

Wagner, S., Breyholz, H. J., Faust, A., Holtke, C., Levkau, B., Schober, O., et al. (2006). Molecular imaging of matrix metalloproteinases in vivo using small molecule inhibitors for SPECT and PET. Current Medicinal Chemistry, 13(23), 2819–2838.CrossRefPubMed

219.

Xu, K., Rajagopal, S., Klebba, I., Dong, S., Ji, Y., Liu, J., et al. (2010). The role of fibroblast Tiam1 in tumor cell invasion and metastasis. Oncogene, 29(50), 6533–6542. https://doi.org/10.1038/onc.2010.385.CrossRefPubMedPubMedCentral

220.

Chang, P. H., Hwang-Verslues, W. W., Chang, Y. C., Chen, C. C., Hsiao, M., Jeng, Y. M., et al. (2012). Activation of Robo1 signaling of breast cancer cells by Slit2 from stromal fibroblast restrains tumorigenesis via blocking PI3K/Akt/beta-catenin pathway. Cancer Research, 72(18), 4652–4661. https://doi.org/10.1158/0008-5472.can-12-0877.CrossRefPubMedPubMedCentral

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Cancer-associated fibroblasts as key regulators of the breast cancer tumor microenvironment

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