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Cancer and Metastasis Reviews

Erschienen in:

11.05.2021

The multifaceted roles of the chemokines CCL2 and CXCL12 in osteophilic metastatic cancers

verfasst von: Élora Midavaine, Jérôme Côté, Philippe Sarret

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 2/2021

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Abstract

Breast and prostate cancers have a great propensity to metastasize to long bones. The development of bone metastases is life-threatening, incurable, and drastically reduces patients’ quality of life. The chemokines CCL2 and CXCL12 and their respective receptors, CCR2 and CXCR4, are central instigators involved in all stages leading to cancer cell dissemination and secondary tumor formation in distant target organs. They orchestrate tumor cell survival, growth and migration, tumor invasion and angiogenesis, and the formation of micrometastases in the bone marrow. The bone niche is of particular importance in metastasis formation, as it expresses high levels of CCL2 and CXCL12, which attract tumor cells and contribute to malignancy. The limited number of available effective treatment strategies highlights the need to better understand the pathophysiology of bone metastases and reduce the skeletal tumor burden in patients diagnosed with metastatic bone disease. This review focuses on the involvement of the CCL2/CCR2 and CXCL12/CXCR4 chemokine axes in the formation and development of bone metastases, as well as on therapeutic perspectives aimed at targeting these chemokine-receptor pairs.

Paget, S. (1989). The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Reviews, 8(2), 98–101.PubMed

Peinado, H., Zhang, H., Matei, I. R., Costa-Silva, B., Hoshino, A., Rodrigues, G., et al. (2017). Pre-metastatic niches: Organ-specific homes for metastases. Nature Reviews Cancer, 17(5), 302–317. https://doi.org/10.1038/nrc.2017.6.CrossRefPubMed

Coleman, R. E. (2001). Metastatic bone disease: Clinical features, pathophysiology and treatment strategies. Cancer Treatment Reviews, 27(3), 165–176. https://doi.org/10.1053/ctrv.2000.0210.CrossRefPubMed

Shah, R. B., Mehra, R., Chinnaiyan, A. M., Shen, R., Ghosh, D., Zhou, M., et al. (2004). Androgen-independent prostate cancer is a heterogeneous group of diseases: Lessons from a rapid autopsy program. Cancer Research, 64(24), 9209–9216. https://doi.org/10.1158/0008-5472.CAN-04-2442.CrossRefPubMed

Wang, J., Loberg, R., & Taichman, R. S. (2006). The pivotal role of CXCL12 (SDF-1)/CXCR4 axis in bone metastasis. Cancer Metastasis Reviews, 25(4), 573–587. https://doi.org/10.1007/s10555-006-9019-x.CrossRefPubMed

Weilbaecher, K. N., Guise, T. A., & McCauley, L. K. (2011). Cancer to bone: A fatal attraction. Nature Reviews. Cancer, 11(6), 411–425. https://doi.org/10.1038/nrc3055.CrossRefPubMed

Clezardin, P., & Teti, A. (2007). Bone metastasis: Pathogenesis and therapeutic implications. Clinical & Experimental Metastasis, 24(8), 599–608. https://doi.org/10.1007/s10585-007-9112-8.CrossRef

Coleman, R. E. (2006). Clinical features of metastatic bone disease and risk of skeletal morbidity. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 12(20 Pt 2), 6243s–6249s. https://doi.org/10.1158/1078-0432.CCR-06-0931.CrossRef

Müller, A., Homey, B., Soto, H., Ge, N., Catron, D., Buchanan, M. E., et al. (2001). Involvement of chemokine receptors in breast cancer metastasis. Nature, 410(6824), 50–56. https://doi.org/10.1038/35065016.CrossRefPubMed

10.

Teicher, B. A., & Fricker, S. P. (2010). CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clinical Cancer Research, 16(11), 2927. https://doi.org/10.1158/1078-0432.CCR-09-2329.CrossRefPubMed

11.

Rucci, N., & Teti, A. (2018). Osteomimicry: How the seed grows in the soil. Calcified Tissue International, 102(2), 131–140. https://doi.org/10.1007/s00223-017-0365-1.CrossRefPubMed

12.

Mundy, G. R. (2002). Metastasis to bone: Causes, consequences and therapeutic opportunities. Nature Reviews Cancer, 2(8), 584–593. https://doi.org/10.1038/nrc867.CrossRefPubMed

13.

Padalecki, S. S., & Guise, T. A. (2002). Actions of bisphosphonates in animal models of breast cancer. Breast Cancer Research, 4(1), 35–41. https://doi.org/10.1186/bcr415.CrossRefPubMed

14.

Bonfil, R. D., Chinni, S., Fridman, R., Kim, H.-R., & Cher, M. L. (2007). Proteases, growth factors, chemokines, and the microenvironment in prostate cancer bone metastasis. Urologic Oncology: Seminars and Original Investigations, 25(5), 407–411. https://doi.org/10.1016/j.urolonc.2007.05.008.CrossRefPubMed

15.

Kitamura, T., Qian, B.-Z., Soong, D., Cassetta, L., Noy, R., Sugano, G., et al. (2015). CCL2-induced chemokine cascade promotes breast cancer metastasis by enhancing retention of metastasis-associated macrophages. The Journal of Experimental Medicine, 212(7), 1043–1059. https://doi.org/10.1084/jem.20141836.CrossRefPubMedPubMedCentral

16.

Vasconcelos, I., Hussainzada, A., Berger, S., Fietze, E., Linke, J., Siedentopf, F., & Schoenegg, W. (2016). The St. Gallen surrogate classification for breast cancer subtypes successfully predicts tumor presenting features, nodal involvement, recurrence patterns and disease free survival. Breast (Edinburgh, Scotland), 29, 181–185. https://doi.org/10.1016/j.breast.2016.07.016.CrossRef

17.

Kondov, B., Milenkovikj, Z., Kondov, G., Petrushevska, G., Basheska, N., Bogdanovska-Todorovska, M., et al. (2018). Presentation of the molecular subtypes of breast cancer detected by immunohistochemistry in surgically treated patients. Open Access Macedonian Journal of Medical Sciences, 6(6), 961–967. https://doi.org/10.3889/oamjms.2018.231.CrossRefPubMedPubMedCentral

18.

Munjal, A., & Leslie, S. W. (2020). Gleason score. In StatPearls. StatPearls Publishing Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK553178/.

19.

Sehn, J. K. (2018). Prostate cancer pathology: Recent updates and controversies. Missouri Medicine, 115(2), 151–155.PubMedPubMedCentral

20.

Zlotnik, A., Burkhardt, A. M., & Homey, B. (2011). Homeostatic chemokine receptors and organ-specific metastasis. Nature Reviews Immunology, 11(9), 597–606. https://doi.org/10.1038/nri3049.CrossRefPubMed

21.

Tanaka, S., Green, S. R., & Quehenberger, O. (2002). Differential expression of the isoforms for the monocyte chemoattractant protein-1 receptor, CCR2, in monocytes. Biochemical and Biophysical Research Communications, 290(1), 73–80. https://doi.org/10.1006/bbrc.2001.6149.CrossRefPubMed

22.

Vicari, A. P., & Caux, C. (2002). Chemokines in cancer. Cytokine & Growth Factor Reviews, 13(2), 143–154. https://doi.org/10.1016/s1359-6101(01)00033-8.CrossRef

23.

Loberg, R. D., Day, L. L., Harwood, J., Ying, C., St. John, L. N., Giles, R., et al. (2006). CCL2 is a potent regulator of prostate cancer cell migration and proliferation. Neoplasia (New York, N.Y.), 8(7), 578–586.CrossRef

24.

Fujimoto, H., Sangai, T., Ishii, G., Ikehara, A., Nagashima, T., Miyazaki, M., & Ochiai, A. (2009). Stromal MCP-1 in mammary tumors induces tumor-associated macrophage infiltration and contributes to tumor progression. International Journal of Cancer, 125(6), 1276–1284. https://doi.org/10.1002/ijc.24378.CrossRefPubMed

25.

Nakashima, E., Mukaida, N., Kubota, Y., Kuno, K., Yasumoto, K., Ichimura, F., et al. (1995). Human MCAF gene transfer enhances the metastatic capacity of a mouse cachectic adenocarcinoma cell line in vivo. Pharmaceutical Research, 12(11), 1598–1604. https://doi.org/10.1023/A:1016276613684.CrossRefPubMed

26.

Greenbaum, A., Hsu, Y.-M. S., Day, R. B., Schuettpelz, L. G., Christopher, M. J., Borgerding, J. N., et al. (2013). CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature, 495(7440), 227–230. https://doi.org/10.1038/nature11926.CrossRefPubMedPubMedCentral

27.

Ma, Q., Jones, D., Borghesani, P. R., Segal, R. A., Nagasawa, T., Kishimoto, T., et al. (1998). Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 95(16), 9448–9453. https://doi.org/10.1073/pnas.95.16.9448.CrossRefPubMedPubMedCentral

28.

Nagasawa, T., Hirota, S., Tachibana, K., Takakura, N., Nishikawa, S., Kitamura, Y., et al. (1996). Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature, 382(6592), 635–638. https://doi.org/10.1038/382635a0.CrossRefPubMed

29.

McGrath, K. E., Koniski, A. D., Maltby, K. M., McGann, J. K., & Palis, J. (1999). Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4. Developmental Biology, 213(2), 442–456. https://doi.org/10.1006/dbio.1999.9405.CrossRefPubMed

30.

Mirshahi, F., Pourtau, J., Li, H., Muraine, M., Trochon, V., Legrand, E., et al. (2000). SDF-1 Activity on microvascular endothelial cells: Consequences on angiogenesis in in vitro and in vivo models. Thrombosis Research, 99(6), 587–594. https://doi.org/10.1016/S0049-3848(00)00292-9.CrossRefPubMed

31.

Balkwill, F. (2004). The significance of cancer cell expression of the chemokine receptor CXCR4. Seminars in Cancer Biology, 14(3), 171–179. https://doi.org/10.1016/j.semcancer.2003.10.003.CrossRefPubMed

32.

Chinni, S. R., Sivalogan, S., Dong, Z., Filho, J. C. T., Deng, X., Bonfil, R. D., & Cher, M. L. (2006). CXCL12/CXCR4 signaling activates Akt-1 and MMP-9 expression in prostate cancer cells: the role of bone microenvironment-associated CXCL12. The Prostate, 66(1), 32–48. https://doi.org/10.1002/pros.20318.CrossRefPubMed

33.

Sun, Y.-X., Wang, J., Shelburne, C. E., Lopatin, D. E., Chinnaiyan, A. M., Rubin, M. A., et al. (2003). Expression of CXCR4 and CXCL12 (SDF-1) in human prostate cancers (PCa) in vivo. Journal of Cellular Biochemistry, 89(3), 462–473. https://doi.org/10.1002/jcb.10522.CrossRefPubMed

34.

Akashi, T., Koizumi, K., Tsuneyama, K., Saiki, I., Takano, Y., & Fuse, H. (2008). Chemokine receptor CXCR4 expression and prognosis in patients with metastatic prostate cancer. Cancer Science, 99(3), 539–542. https://doi.org/10.1111/j.1349-7006.2007.00712.x.CrossRefPubMed

35.

Zhao, H., Guo, L., Zhao, H., Zhao, J., Weng, H., & Zhao, B. (2014). CXCR4 over-expression and survival in cancer: A system review and meta-analysis. Oncotarget, 6(7), 5022–5040.CrossRefPubMedCentral

36.

Lee, J. Y., Kang, D. H., Chung, D. Y., Kwon, J. K., Lee, H., Cho, N. H., et al. (2014). Meta-analysis of the relationship between CXCR4 expression and metastasis in prostate cancer. The World Journal of Men’s Health, 32(3), 167–175. https://doi.org/10.5534/wjmh.2014.32.3.167.CrossRefPubMedPubMedCentral

37.

van Furth, R., & Cohn, Z. A. (1968). The origin and kinetics of mononuclear phagocytes. The Journal of Experimental Medicine, 128(3), 415–435.CrossRefPubMedPubMedCentral

38.

Geissmann, F., Jung, S., & Littman, D. R. (2003). Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity, 19(1), 71–82. https://doi.org/10.1016/s1074-7613(03)00174-2.CrossRefPubMed

39.

Serbina, N. V., & Pamer, E. G. (2006). Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nature Immunology, 7(3), 311–317. https://doi.org/10.1038/ni1309.CrossRefPubMed

40.

Yona, S., Kim, K.-W., Wolf, Y., Mildner, A., Varol, D., Breker, M., et al. (2013). Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity, 38(1), 79–91. https://doi.org/10.1016/j.immuni.2012.12.001.CrossRefPubMed

41.

Teh, Y. C., Ding, J. L., Ng, L. G., & Chong, S. Z. (2019). Capturing the fantastic voyage of monocytes through time and space. Frontiers in Immunology, 10, 834. https://doi.org/10.3389/fimmu.2019.00834.CrossRefPubMedPubMedCentral

42.

Katayama, Y., Battista, M., Kao, W.-M., Hidalgo, A., Peired, A. J., Thomas, S. A., & Frenette, P. S. (2006). Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell, 124(2), 407–421. https://doi.org/10.1016/j.cell.2005.10.041.CrossRefPubMed

43.

Chong, S. Z., Evrard, M., Devi, S., Chen, J., Lim, J. Y., See, P., et al. (2016). CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses. The Journal of Experimental Medicine, 213(11), 2293–2314. https://doi.org/10.1084/jem.20160800.CrossRefPubMedPubMedCentral

44.

Bonapace, L., Coissieux, M.-M., Wyckoff, J., Mertz, K. D., Varga, Z., Junt, T., & Bentires-Alj, M. (2014). Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis. Nature, 515(7525), 130–133. https://doi.org/10.1038/nature13862.CrossRefPubMed

45.

Auffray, C., Fogg, D., Garfa, M., Elain, G., Join-Lambert, O., Kayal, S., et al. (2007). Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science (New York, N.Y.), 317(5838), 666–670. https://doi.org/10.1126/science.1142883.CrossRef

46.

Ginhoux, F., & Guilliams, M. (2016). Tissue-resident macrophage ontogeny and homeostasis. Immunity, 44(3), 439–449 http://dx.doi.org.ezproxy.usherbrooke.ca/10.1016/j.immuni.2016.02.024.CrossRefPubMed

47.

Shi, C., & Pamer, E. G. (2011). Monocyte recruitment during infection and inflammation. Nature Reviews. Immunology, 11(11), 762–774. https://doi.org/10.1038/nri3070.CrossRefPubMedPubMedCentral

48.

Qian, B.-Z., & Pollard, J. W. (2010). Macrophage diversity enhances tumor progression and metastasis. Cell, 141(1), 39–51. https://doi.org/10.1016/j.cell.2010.03.014.CrossRefPubMedPubMedCentral

49.

Wellenstein, M. D., & de Visser, K. E. (2018). Cancer-cell-intrinsic mechanisms shaping the tumor immune landscape. Immunity, 48(3), 399–416. https://doi.org/10.1016/j.immuni.2018.03.004.CrossRefPubMed

50.

Bingle, L., Brown, N. J., & Lewis, C. E. (2002). The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. The Journal of Pathology, 196(3), 254–265. https://doi.org/10.1002/path.1027.CrossRefPubMed

51.

DeNardo, D. G., Brennan, D. J., Rexhepaj, E., Ruffell, B., Shiao, S. L., Madden, S. F., et al. (2011). Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discovery, 1, 54–67. https://doi.org/10.1158/2159-8274.CD-10-0028.CrossRefPubMedPubMedCentral

52.

Gentles, A. J., Newman, A. M., Liu, C. L., Bratman, S. V., Feng, W., Kim, D., et al. (2015). The prognostic landscape of genes and infiltrating immune cells across human cancers. Nature Medicine, 21(8), 938–945. https://doi.org/10.1038/nm.3909.CrossRefPubMedPubMedCentral

53.

Raskov, H., Orhan, A., Christensen, J. P., & Gögenur, I. (2020). Cytotoxic CD8 + T cells in cancer and cancer immunotherapy. British Journal of Cancer, 1–9. https://doi.org/10.1038/s41416-020-01048-4.

54.

Doedens, A. L., Stockmann, C., Rubinstein, M. P., Liao, D., Zhang, N., DeNardo, D. G., et al. (2010). Macrophage expression of hypoxia-inducible factor-1 alpha suppresses T-cell function and promotes tumor progression. Cancer Research, 70(19), 7465–7475. https://doi.org/10.1158/0008-5472.CAN-10-1439.CrossRefPubMedPubMedCentral

55.

Gordon, S., & Plüddemann, A. (2019). The mononuclear phagocytic system. Generation of Diversity. Frontiers in Immunology, 10. https://doi.org/10.3389/fimmu.2019.01893.

56.

Gabrilovich, D. I. (2017). Myeloid-derived suppressor cells. Cancer Immunology Research, 5(1), 3–8. https://doi.org/10.1158/2326-6066.CIR-16-0297.CrossRefPubMedPubMedCentral

57.

Corzo, C. A., Condamine, T., Lu, L., Cotter, M. J., Youn, J.-I., Cheng, P., et al. (2010). HIF-1α regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. The Journal of Experimental Medicine, 207(11), 2439–2453. https://doi.org/10.1084/jem.20100587.CrossRefPubMedPubMedCentral

58.

Cassetta, L., Fragkogianni, S., Sims, A. H., Swierczak, A., Forrester, L. M., Zhang, H., et al. (2019). Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers, and therapeutic targets. Cancer Cell, 35(4), 588–602.e10. https://doi.org/10.1016/j.ccell.2019.02.009.CrossRefPubMedPubMedCentral

59.

Dutrochet, H. (1824). Recherches anatomiques et physiologiques sur la structure intime des animaux et des végétaux, et sur leur motilité. J.B. Baillière.

60.

Ley, K., Laudanna, C., Cybulsky, M. I., & Nourshargh, S. (2007). Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nature Reviews Immunology, 7(9), 678–689. https://doi.org/10.1038/nri2156.CrossRefPubMed

61.

Lu, X., & Kang, Y. (2009). Chemokine (C-C motif) ligand 2 engages CCR2+ stromal cells of monocytic origin to promote breast cancer metastasis to lung and bone. The Journal of Biological Chemistry, 284(42), 29087–29096. https://doi.org/10.1074/jbc.M109.035899.CrossRefPubMedPubMedCentral

62.

Solinas, G., Germano, G., Mantovani, A., & Allavena, P. (2009). Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. Journal of Leukocyte Biology, 86(5), 1065–1073. https://doi.org/10.1189/jlb.0609385.CrossRefPubMed

63.

Roblek, M., Protsyuk, D., Becker, P. F., Stefanescu, C., Gorzelanny, C., Glaus Garzon, J. F., et al. (2019). CCL2 is a vascular permeability factor inducing CCR2-dependent endothelial retraction during lung metastasis. Molecular Cancer Research, 17(3), 783–793. https://doi.org/10.1158/1541-7786.MCR-18-0530.CrossRefPubMed

64.

Roca, H., Varsos, Z. S., Sud, S., Craig, M. J., Ying, C., & Pienta, K. J. (2009). CCL2 and interleukin-6 promote survival of human CD11b+ peripheral blood mononuclear cells and induce M2-type macrophage polarization. The Journal of Biological Chemistry, 284(49), 34342–34354. https://doi.org/10.1074/jbc.M109.042671.CrossRefPubMedPubMedCentral

65.

Leek, R. D., Lewis, C. E., Whitehouse, R., Greenall, M., Clarke, J., & Harris, A. L. (1996). Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Research, 56(20), 4625–4629.PubMed

66.

Li, D., Ji, H., Niu, X., Yin, L., Wang, Y., Gu, Y., et al. (2020). Tumor-associated macrophages secrete CC-chemokine ligand 2 and induce tamoxifen resistance by activating PI3K/Akt/mTOR in breast cancer. Cancer Science, 111(1), 47–58. https://doi.org/10.1111/cas.14230.CrossRefPubMed

67.

Ahirwar, D. K., Nasser, M. W., Ouseph, M. M., Elbaz, M., Cuitiño, M. C., Kladney, R. D., et al. (2018). Fibroblast-derived CXCL12 promotes breast cancer metastasis by facilitating tumor cell intravasation. Oncogene, 37(32), 4428–4442. https://doi.org/10.1038/s41388-018-0263-7.CrossRefPubMedPubMedCentral

68.

Wang, Z., Ma, Y., Yu, X., Niu, Q., Han, Z., Wang, H., et al. (2018). Targeting CXCR4–CXCL12 axis for visualizing, predicting, and inhibiting breast cancer metastasis with theranostic AMD3100–Ag2S quantum dot probe. Advanced Functional Materials, 28(23), 1800732. https://doi.org/10.1002/adfm.201800732.CrossRef

69.

Darash-Yahana, M., Pikarsky, E., Abramovitch, R., Zeira, E., Pal, B., Karplus, R., et al. (2004). Role of high expression levels of CXCR4 in tumor growth, vascularization, and metastasis. The FASEB Journal, 18(11), 1240–1242. https://doi.org/10.1096/fj.03-0935fje.CrossRefPubMed

70.

Devignes, C.-S., Aslan, Y., Brenot, A., Devillers, A., Schepers, K., Fabre, S., et al. (2018). HIF signaling in osteoblast-lineage cells promotes systemic breast cancer growth and metastasis in mice. Proceedings of the National Academy of Sciences, 115(5), E992–E1001. https://doi.org/10.1073/pnas.1718009115.CrossRef

71.

Guo, M., Cai, C., Zhao, G., Qiu, X., Zhao, H., Ma, Q., et al. (2014). Hypoxia promotes migration and induces CXCR4 expression via HIF-1α activation in human osteosarcoma. PLoS One, 9(3). https://doi.org/10.1371/journal.pone.0090518.

72.

Schioppa, T., Uranchimeg, B., Saccani, A., Biswas, S. K., Doni, A., Rapisarda, A., et al. (2003). Regulation of the chemokine receptor CXCR4 by hypoxia. The Journal of Experimental Medicine, 198(9), 1391–1402. https://doi.org/10.1084/jem.20030267.CrossRefPubMedPubMedCentral

73.

Zagzag, D., Lukyanov, Y., Lan, L., Ali, M. A., Esencay, M., Mendez, O., et al. (2006). Hypoxia-inducible factor 1 and VEGF upregulate CXCR4 in glioblastoma: implications for angiogenesis and glioma cell invasion. Laboratory Investigation, 86(12), 1221–1232. https://doi.org/10.1038/labinvest.3700482.CrossRefPubMed

74.

Knowles, H. J., & Harris, A. L. (2007). Macrophages and the hypoxic tumour microenvironment. Frontiers in Bioscience: a Journal and Virtual Library, 12, 4298–4314. https://doi.org/10.2741/2389.CrossRef

75.

Bleul, C. C., Fuhlbrigge, R. C., Casasnovas, J. M., Aiuti, A., & Springer, T. A. (1996). A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). The Journal of Experimental Medicine, 184(3), 1101–1109. https://doi.org/10.1084/jem.184.3.1101.CrossRefPubMed

76.

Burger, J. A., Burger, M., & Kipps, T. J. (1999). Chronic lymphocytic leukemia B cells express functional CXCR4 chemokine receptors that mediate spontaneous migration beneath bone marrow stromal cells. Blood, 94(11), 3658–3667.CrossRefPubMed

77.

Sun, X., Cheng, G., Hao, M., Zheng, J., Zhou, X., Zhang, J., et al. (2010). CXCL12 / CXCR4 / CXCR7 chemokine axis and cancer progression. Cancer and Metastasis Reviews, 29(4), 709–722. https://doi.org/10.1007/s10555-010-9256-x.CrossRefPubMed

78.

Brigati, C., Noonan, D. M., Albini, A., & Benelli, R. (2002). Tumors and inflammatory infiltrates: friends or foes? Clinical & Experimental Metastasis, 19(3), 247–258. https://doi.org/10.1023/a:1015587423262.CrossRef

79.

Saji, H., Koike, M., Yamori, T., Saji, S., Seiki, M., Matsushima, K., & Toi, M. (2001). Significant correlation of monocyte chemoattractant protein-1 expression with neovascularization and progression of breast carcinoma. Cancer, 92(5), 1085–1091. https://doi.org/10.1002/1097-0142(20010901)92:5<1085::aid-cncr1424>3.0.co;2-k.

80.

Walter, S., Bottazzi, B., Govoni, D., Colotta, F., & Mantovani, A. (1991). Macrophage infiltration and growth of sarcoma clones expressing different amounts of monocyte chemotactic protein/JE. International Journal of Cancer, 49(3), 431–435. https://doi.org/10.1002/ijc.2910490321.CrossRefPubMed

81.

Ueno, T., Toi, M., Saji, H., Muta, M., Bando, H., Kuroi, K., et al. (2000). Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer. Clinical Cancer Research, 6(8), 3282–3289.PubMed

82.

Grivennikov, S. I., Greten, F. R., & Karin, M. (2010). Immunity, inflammation, and cancer. Cell, 140(6), 883–899. https://doi.org/10.1016/j.cell.2010.01.025.CrossRefPubMedPubMedCentral

83.

Fang, W. B., Jokar, I., Zou, A., Lambert, D., Dendukuri, P., & Cheng, N. (2012). CCL2/CCR2 chemokine signaling coordinates survival and motility of breast cancer cells through Smad3 Protein- and p42/44 mitogen-activated protein kinase (MAPK)-dependent mechanisms *. Journal of Biological Chemistry, 287(43), 36593–36608. https://doi.org/10.1074/jbc.M112.365999.CrossRef

84.

Fang, W. B., Yao, M., Brummer, G., Acevedo, D., Alhakamy, N., Berkland, C., & Cheng, N. (2016). Targeted gene silencing of CCL2 inhibits triple negative breast cancer progression by blocking cancer stem cell renewal and M2 macrophage recruitment. Oncotarget, 7(31), 49349–49367. https://doi.org/10.18632/oncotarget.9885.CrossRefPubMedPubMedCentral

85.

Li, M., Knight, D. A. A., Snyder, L., Smyth, M. J., & Stewart, T. J. (2013). A role for CCL2 in both tumor progression and immunosurveillance. Oncoimmunology, 2(7). https://doi.org/10.4161/onci.25474.

86.

Lu, Y., Cai, Z., Xiao, G., Liu, Y., Keller, E. T., Yao, Z., & Zhang, J. (2007). CCR2 expression correlates with prostate cancer progression. Journal of Cellular Biochemistry, 101(3), 676–685. https://doi.org/10.1002/jcb.21220.CrossRefPubMed

87.

Lu, Y., Cai, Z., Galson, D. L., Xiao, G., Liu, Y., George, D. E., et al. (2006). Monocyte chemotactic protein-1 (MCP-1) acts as a paracrine and autocrine factor for prostate cancer growth and invasion. The Prostate, 66(12), 1311–1318. https://doi.org/10.1002/pros.20464.CrossRefPubMed

88.

Lavender, N., Yang, J., Chen, S.-C., Sai, J., Johnson, C. A., Owens, P., et al. (2017). The Yin/Yan of CCL2: a minor role in neutrophil anti-tumor activity in vitro but a major role on the outgrowth of metastatic breast cancer lesions in the lung in vivo. BMC Cancer, 17(1), 88. https://doi.org/10.1186/s12885-017-3074-2.CrossRefPubMedPubMedCentral

89.

Nesbit, M., Schaider, H., Miller, T. H., & Herlyn, M. (2001). Low-level monocyte chemoattractant protein-1 stimulation of monocytes leads to tumor formation in nontumorigenic melanoma cells. Journal of Immunology (Baltimore, Md. : 1950), 166(11), 6483–6490. https://doi.org/10.4049/jimmunol.166.11.6483.CrossRef

90.

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

91.

Chen, X., Wang, Y., Nelson, D., Tian, S., Mulvey, E., Patel, B., et al. (2016). CCL2/CCR2 regulates the tumor microenvironment in HER-2/neu-driven mammary carcinomas in mice. PLoS One, 11(11), e0165595. https://doi.org/10.1371/journal.pone.0165595.CrossRefPubMedPubMedCentral

92.

Loberg, R. D., Ying, C., Craig, M., Day, L. L., Sargent, E., Neeley, C., et al. (2007). Targeting CCL2 with systemic delivery of neutralizing antibodies induces prostate cancer tumor regression in vivo. Cancer Research, 67(19), 9417–9424. https://doi.org/10.1158/0008-5472.CAN-07-1286.CrossRefPubMed

93.

Fang, W. B., Yao, M., Jokar, I., Alhakamy, N., Berkland, C., Chen, J., et al. (2015). The CCL2 chemokine is a negative regulator of autophagy and necrosis in luminal B breast cancer cells. Breast Cancer Research and Treatment, 150(2), 309–320. https://doi.org/10.1007/s10549-015-3324-4.CrossRefPubMedPubMedCentral

94.

Fein, M. R., He, X.-Y., Almeida, A. S., Bružas, E., Pommier, A., Yan, R., et al. (2020). Cancer cell CCR2 orchestrates suppression of the adaptive immune response. Journal of Experimental Medicine, 217(10), e20181551. https://doi.org/10.1084/jem.20181551.CrossRef

95.

Kersten, K., Coffelt, S. B., Hoogstraat, M., Verstegen, N. J. M., Vrijland, K., Ciampricotti, M., et al. (2017). Mammary tumor-derived CCL2 enhances pro-metastatic systemic inflammation through upregulation of IL1β in tumor-associated macrophages. OncoImmunology, 6(8), e1334744. https://doi.org/10.1080/2162402X.2017.1334744.CrossRefPubMedPubMedCentral

96.

Kudo-Saito, C., Shirako, H., Ohike, M., Tsukamoto, N., & Kawakami, Y. (2013). CCL2 is critical for immunosuppression to promote cancer metastasis. Clinical & Experimental Metastasis, 30(4), 393–405. https://doi.org/10.1007/s10585-012-9545-6.CrossRef

97.

Peng, L., Shu, S., & Krauss, J. C. (1997). Monocyte chemoattractant protein inhibits the generation of tumor-reactive T cells. Cancer Research, 57(21), 4849–4854.PubMed

98.

Conti, I., & Rollins, B. J. (2004). CCL2 (monocyte chemoattractant protein-1) and cancer. Seminars in Cancer Biology, 14(3), 149–154. https://doi.org/10.1016/j.semcancer.2003.10.009.CrossRefPubMed

99.

Jordan, J. T., Sun, W., Hussain, S. F., DeAngulo, G., Prabhu, S. S., & Heimberger, A. B. (2008). Preferential migration of regulatory T cells mediated by glioma-secreted chemokines can be blocked with chemotherapy. Cancer Immunology, Immunotherapy, 57(1), 123–131. https://doi.org/10.1007/s00262-007-0336-x.CrossRefPubMed

100.

Terwey, T. H., Kim, T. D., Kochman, A. A., Hubbard, V. M., Lu, S., Zakrzewski, J. L., et al. (2005). CCR2 is required for CD8-induced graft-versus-host disease. Blood, 106(9), 3322–3330. https://doi.org/10.1182/blood-2005-05-1860.CrossRefPubMedPubMedCentral

101.

Barbero, S., Bonavia, R., Bajetto, A., Porcile, C., Pirani, P., Ravetti, J. L., et al. (2003). Stromal cell-derived factor 1alpha stimulates human glioblastoma cell growth through the activation of both extracellular signal-regulated kinases 1/2 and Akt. Cancer Research, 63(8), 1969–1974.PubMed

102.

Begley, L. A., MacDonald, J. W., Day, M. L., & Macoska, J. A. (2007). CXCL12 activates a robust transcriptional response in human prostate epithelial cells. Journal of Biological Chemistry, 282(37), 26767–26774. https://doi.org/10.1074/jbc.M700440200.CrossRef

103.

Vlahakis, S. R., Villasis-Keever, A., Gomez, T., Vanegas, M., Vlahakis, N., & Paya, C. V. (2002). G protein-coupled chemokine receptors induce both survival and apoptotic signaling pathways. Journal of Immunology (Baltimore, Md. : 1950), 169(10), 5546–5554. https://doi.org/10.4049/jimmunol.169.10.5546.CrossRef

104.

Hall, J. M., & Korach, K. S. (2003). Stromal cell-derived factor 1, a novel target of estrogen receptor action, mediates the mitogenic effects of estradiol in ovarian and breast cancer cells. Molecular Endocrinology, 17(5), 792–803. https://doi.org/10.1210/me.2002-0438.CrossRefPubMed

105.

Hsu, E. L., Yoon, D., Choi, H. H., Wang, F., Taylor, R. T., Chen, N., et al. (2007). A proposed mechanism for the protective effect of dioxin against breast cancer. Toxicological Sciences: An Official Journal of the Society of Toxicology, 98(2), 436–444. https://doi.org/10.1093/toxsci/kfm125.CrossRef

106.

Cai, J., Kandagatla, P., Singareddy, R., Kropinski, A., Sheng, S., Cher, M. L., & Chinni, S. R. (2010). Androgens induce functional CXCR4 through ERG factor expression in TMPRSS2-ERG fusion-positive prostate cancer cells. Translational Oncology, 3(3), 195–203. https://doi.org/10.1593/tlo.09328.CrossRefPubMedPubMedCentral

107.

Azariadis, K., Kiagiadaki, F., Pelekanou, V., Bempi, V., Alexakis, K., Kampa, M., et al. (2017). Androgen triggers the pro-migratory CXCL12/CXCR4 axis in AR-positive breast cancer cell lines: underlying mechanism and possible implications for the use of aromatase inhibitors in breast cancer. Cellular Physiology and Biochemistry, 44(1), 66–84. https://doi.org/10.1159/000484584.CrossRefPubMed

108.

Domanska, U. M., Timmer-Bosscha, H., Nagengast, W. B., Oude Munnink, T. H., Kruizinga, R. C., Ananias, H. J. K., et al. (2012). CXCR4 inhibition with AMD3100 sensitizes prostate cancer to docetaxel chemotherapy. Neoplasia, 14(8), 709–718. https://doi.org/10.1593/neo.12324.CrossRefPubMedPubMedCentral

109.

Luker, K. E., Lewin, S. A., Mihalko, L. A., Schmidt, B. T., Winkler, J. S., Coggins, N. L., et al. (2012). Scavenging of CXCL12 by CXCR7 promotes tumor growth and metastasis of CXCR4-positive breast cancer cells. Oncogene, 31(45), 4750–4758. https://doi.org/10.1038/onc.2011.633.CrossRefPubMedPubMedCentral

110.

Yan, M., Jene, N., Byrne, D., Millar, E. K., O’Toole, S. A., McNeil, C. M., et al. (2011). Recruitment of regulatory T cells is correlated with hypoxia-induced CXCR4 expression, and is associated with poor prognosis in basal-like breast cancers. Breast Cancer Research : BCR, 13(2), R47. https://doi.org/10.1186/bcr2869.CrossRefPubMedPubMedCentral

111.

Lyden, D., Hattori, K., Dias, S., Costa, C., Blaikie, P., Butros, L., et al. (2001). Impaired recruitment of bone-marrow–derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nature Medicine, 7(11), 1194–1201. https://doi.org/10.1038/nm1101-1194.CrossRefPubMed

112.

Kakinuma, T., & Hwang, S. T. (2006). Chemokines, chemokine receptors, and cancer metastasis. Journal of Leukocyte Biology, 79(4), 639–651. https://doi.org/10.1189/jlb.1105633.CrossRefPubMed

113.

Strieter, R. M., Polverini, P. J., Kunkel, S. L., Arenberg, D. A., Burdick, M. D., Kasper, J., et al. (1995). The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. Journal of Biological Chemistry, 270(45), 27348–27357. https://doi.org/10.1074/jbc.270.45.27348.CrossRef

114.

Li, X., Loberg, R., Liao, J., Ying, C., Snyder, L. A., Pienta, K. J., & McCauley, L. K. (2009). A destructive cascade mediated by CCL2 facilitates prostate cancer growth in bone. Cancer Research, 69(4), 1685–1692. https://doi.org/10.1158/0008-5472.CAN-08-2164.CrossRefPubMedPubMedCentral

115.

Salcedo, R., Ponce, M. L., Young, H. A., Wasserman, K., Ward, J. M., Kleinman, H. K., et al. (2000). Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression. Blood, 96(1), 34–40.CrossRefPubMed

116.

Knowles, H., Leek, R., & Harris, A. L. (2004). Macrophage infiltration and angiogenesis in human malignancy. Novartis Foundation Symposium, 256, 189–200 discussion 200-204, 259–269.PubMed

117.

Kryczek, I., Wei, S., Keller, E., Liu, R., & Zou, W. (2007). Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis. American Journal of Physiology. Cell Physiology, 292(3), C987–C995. https://doi.org/10.1152/ajpcell.00406.2006.CrossRefPubMed

118.

Takahashi, T., Kalka, C., Masuda, H., Chen, D., Silver, M., Kearney, M., et al. (1999). Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nature Medicine, 5(4), 434–438. https://doi.org/10.1038/7434.CrossRefPubMed

119.

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

120.

Kawakami, Y., Ii, M., Matsumoto, T., Kuroda, R., Kuroda, T., Kwon, S.-M., et al. (2015). SDF-1/CXCR4 axis in Tie2-lineage cells including endothelial progenitor cells contributes to bone fracture healing. Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research, 30(1), 95–105. https://doi.org/10.1002/jbmr.2318.CrossRef

121.

Yamaguchi, J., Kusano, K. F., Masuo, O., Kawamoto, A., Silver, M., Murasawa, S., et al. (2003). Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation, 107(9), 1322–1328. https://doi.org/10.1161/01.cir.0000055313.77510.22.CrossRefPubMed

122.

Giampieri, S., Manning, C., Hooper, S., Jones, L., Hill, C. S., & Sahai, E. (2009). Localised and reversible TGFβ signalling switches breast cancer cells from cohesive to single cell motility. Nature Cell Biology, 11(11), 1287–1296. https://doi.org/10.1038/ncb1973.CrossRefPubMedPubMedCentral

123.

Pang, M.-F., Georgoudaki, A.-M., Lambut, L., Johansson, J., Tabor, V., Hagikura, K., et al. (2016). TGF-β1-induced EMT promotes targeted migration of breast cancer cells through the lymphatic system by the activation of CCR7/CCL21-mediated chemotaxis. Oncogene, 35(6), 748–760. https://doi.org/10.1038/onc.2015.133.CrossRefPubMed

124.

Xu, J., Lamouille, S., & Derynck, R. (2009). TGF-β-induced epithelial to mesenchymal transition. Cell Research, 19(2), 156–172. https://doi.org/10.1038/cr.2009.5.CrossRefPubMed

125.

Shi, C.-L., Yu, C.-H., Zhang, Y., Zhao, D., Chang, X.-H., & Wang, W.-H. (2011). Monocyte chemoattractant protein-1 modulates invasion and apoptosis of PC-3M prostate cancer cells via regulating expression of VEGF, MMP9 and caspase-3. Asian Pacific Journal of Cancer Prevention : APJCP, 12(2), 555–559.PubMed

126.

Qian, B., Deng, Y., Im, J. H., Muschel, R. J., Zou, Y., Li, J., et al. (2009). A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. PLoS One, 4(8), e6562. https://doi.org/10.1371/journal.pone.0006562.CrossRefPubMedPubMedCentral

127.

Harney, A. S., Arwert, E. N., Entenberg, D., Wang, Y., Guo, P., Qian, B.-Z., et al. (2015). Real-time imaging reveals local, transient vascular permeability and tumor cell intravasation stimulated by Tie2Hi macrophage-derived VEGFA. Cancer Discovery, 5(9), 932–943. https://doi.org/10.1158/2159-8290.CD-15-0012.CrossRefPubMedPubMedCentral

128.

Wyckoff, J. B., Wang, Y., Lin, E. Y., Li, J., Goswami, S., Stanley, E. R., et al. (2007). Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Research, 67(6), 2649–2656. https://doi.org/10.1158/0008-5472.CAN-06-1823.CrossRefPubMed

129.

Roh-Johnson, M., Bravo-Cordero, J. J., Patsialou, A., Sharma, V. P., Guo, P., Liu, H., et al. (2014). Macrophage contact induces RhoA GTPase signaling to trigger tumor cell intravasation. Oncogene, 33(33), 4203–4212. https://doi.org/10.1038/onc.2013.377.CrossRefPubMed

130.

Zhang, X. H.-F., Jin, X., Malladi, S., Zou, Y., Wen, Y. H., Brogi, E., et al. (2013). Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma. Cell, 154(5), 1060–1073. https://doi.org/10.1016/j.cell.2013.07.036.CrossRefPubMedPubMedCentral

131.

Helbig, G., Christopherson, K. W., Bhat-Nakshatri, P., Kumar, S., Kishimoto, H., Miller, K. D., et al. (2003). NF-κ B promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4. Journal of Biological Chemistry, 278(24), 21631–21638. https://doi.org/10.1074/jbc.M300609200.CrossRef

132.

Fernandis, A. Z., Prasad, A., Band, H., Klösel, R., & Ganju, R. K. (2004). Regulation of CXCR4-mediated chemotaxis and chemoinvasion of breast cancer cells. Oncogene, 23(1), 157–167. https://doi.org/10.1038/sj.onc.1206910.CrossRefPubMed

133.

Singh, S., Singh, U. P., Grizzle, W. E., & Lillard, J. W. (2004). CXCL12-CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion. Laboratory Investigation; a Journal of Technical Methods and Pathology, 84(12), 1666–1676. https://doi.org/10.1038/labinvest.3700181.CrossRefPubMed

134.

Engl, T., Relja, B., Marian, D., Blumenberg, C., Müller, I., Beecken, W.-D., et al. (2006). CXCR4 chemokine receptor mediates prostate tumor cell adhesion through α5 and β3 integrins. Neoplasia, 8(4), 290–301. https://doi.org/10.1593/neo.05694.CrossRefPubMedPubMedCentral

135.

Fujita, M., Davari, P., Takada, Y. K., & Takada, Y. (2018). Stromal cell-derived factor-1 (CXCL12) activates integrins by direct binding to an allosteric ligand-binding site (site 2) of integrins without CXCR4. The Biochemical Journal, 475(4), 723–732. https://doi.org/10.1042/BCJ20170867.CrossRefPubMed

136.

Sun, Y.-X., Fang, M., Wang, J., Cooper, C. R., Pienta, K. J., & Taichman, R. S. (2007). Expression and activation of alpha v beta 3 integrins by SDF-1/CXC12 increases the aggressiveness of prostate cancer cells. The Prostate, 67(1), 61–73. https://doi.org/10.1002/pros.20500.CrossRefPubMed

137.

Sanz-Rodríguez, F., Hidalgo, A., & Teixidó, J. (2001). Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1/fibronectin and VCAM-1. Blood, 97(2), 346–351. https://doi.org/10.1182/blood.v97.2.346.CrossRefPubMed

138.

Becker, A., Thakur, B. K., Weiss, J. M., Kim, H. S., Peinado, H., & Lyden, D. (2016). Extracellular vesicles in cancer: Cell-to-cell mediators of metastasis. Cancer Cell, 30(6), 836–848. https://doi.org/10.1016/j.ccell.2016.10.009.CrossRefPubMedPubMedCentral

139.

Guo, Y., Ji, X., Liu, J., Fan, D., Zhou, Q., Chen, C., et al. (2019). Effects of exosomes on pre-metastatic niche formation in tumors. Molecular Cancer, 18(1), 39. https://doi.org/10.1186/s12943-019-0995-1.CrossRefPubMedPubMedCentral

140.

Kaplan, R. N., Rafii, S., & Lyden, D. (2006). Preparing the “soil”: The premetastatic niche. Cancer Research, 66(23), 11089–11093. https://doi.org/10.1158/0008-5472.CAN-06-2407.CrossRefPubMedPubMedCentral

141.

Zeng, Z., Li, Y., Pan, Y., Lan, X., Song, F., Sun, J., et al. (2018). Cancer-derived exosomal miR-25-3p promotes pre-metastatic niche formation by inducing vascular permeability and angiogenesis. Nature Communications, 9(1), 5395. https://doi.org/10.1038/s41467-018-07810-w.CrossRefPubMedPubMedCentral

142.

Zhou, W., Fong, M. Y., Min, Y., Somlo, G., Liu, L., Palomares, M. R., et al. (2014). Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell, 25(4), 501–515. https://doi.org/10.1016/j.ccr.2014.03.007.CrossRefPubMedPubMedCentral

143.

Kang, S.-A., Hasan, N., Mann, A. P., Zheng, W., Zhao, L., Morris, L., et al. (2015). Blocking the adhesion cascade at the premetastatic niche for prevention of breast cancer metastasis. Molecular Therapy, 23(6), 1044–1054. https://doi.org/10.1038/mt.2015.45.CrossRefPubMedPubMedCentral

144.

Wang, J. M., Deng, X., Gong, W., & Su, S. (1998). Chemokines and their role in tumor growth and metastasis. Journal of Immunological Methods, 220(1–2), 1–17. https://doi.org/10.1016/s0022-1759(98)00128-8.CrossRefPubMed

145.

Wang, S., Li, G.-X., Tan, C.-C., He, R., Kang, L.-J., Lu, J.-T., et al. (2019). FOXF2 reprograms breast cancer cells into bone metastasis seeds. Nature Communications, 10(1), 2707. https://doi.org/10.1038/s41467-019-10379-7.CrossRefPubMedPubMedCentral

146.

Figenschau, S. L., Knutsen, E., Urbarova, I., Fenton, C., Elston, B., Perander, M., et al. (2018). ICAM1 expression is induced by proinflammatory cytokines and associated with TLS formation in aggressive breast cancer subtypes. Scientific Reports, 8(1), 11720. https://doi.org/10.1038/s41598-018-29604-2.CrossRefPubMedPubMedCentral

147.

Rosette, C., Roth, R. B., Oeth, P., Braun, A., Kammerer, S., Ekblom, J., & Denissenko, M. F. (2005). Role of ICAM1 in invasion of human breast cancer cells. Carcinogenesis, 26(5), 943–950. https://doi.org/10.1093/carcin/bgi070.CrossRefPubMed

148.

Graves, D. T., Jiang, Y., & Valente, A. J. (1999). The expression of monocyte chemoattractant protein-1 and other chemokines by osteoblasts. Frontiers in Bioscience: a Journal and Virtual Library, 4, D571–D580. https://doi.org/10.2741/graves.CrossRef

149.

Khan, U. A., Hashimi, S. M., Bakr, M. M., Forwood, M. R., & Morrison, N. A. (2016). CCL2 and CCR2 are essential for the formation of osteoclasts and foreign body giant cells. Journal of Cellular Biochemistry, 117(2), 382–389. https://doi.org/10.1002/jcb.25282.CrossRefPubMed

150.

Youngs, S. J., Ali, S. A., Taub, D. D., & Rees, R. C. (1997). Chemokines induce migrational responses in human breast carcinoma cell lines. International Journal of Cancer, 71(2), 257–266. https://doi.org/10.1002/(sici)1097-0215(19970410)71:2<257::aid-ijc22>3.0.co;2-d.

151.

Terashima, Y., Onai, N., Murai, M., Enomoto, M., Poonpiriya, V., Hamada, T., et al. (2005). Pivotal function for cytoplasmic protein FROUNT in CCR2-mediated monocyte chemotaxis. Nature Immunology, 6(8), 827–835. https://doi.org/10.1038/ni1222.CrossRefPubMed

152.

van Golen, K. L., Ying, C., Sequeira, L., Dubyk, C. W., Reisenberger, T., Chinnaiyan, A. M., et al. (2008). CCL2 induces prostate cancer transendothelial cell migration via activation of the small GTPase Rac. Journal of Cellular Biochemistry, 104(5), 1587–1597. https://doi.org/10.1002/jcb.21652.CrossRefPubMed

153.

Ochoa, O., Sun, D., Reyes-Reyna, S. M., Waite, L. L., Michalek, J. E., McManus, L. M., & Shireman, P. K. (2007). Delayed angiogenesis and VEGF production in CCR2−/− mice during impaired skeletal muscle regeneration. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 293(2), R651–R661. https://doi.org/10.1152/ajpregu.00069.2007.CrossRefPubMed

154.

Mohan, S., & Baylink, D. J. (1991). Bone growth factors. Clinical Orthopaedics and Related Research, 263, 30–48.

155.

Solheim, E. (1998). Growth factors in bone. International Orthopaedics, 22(6), 410–416. https://doi.org/10.1007/s002640050290.CrossRefPubMedPubMedCentral

156.

Liang, Z., Wu, T., Lou, H., Yu, X., Taichman, R. S., Lau, S. K., et al. (2004). Inhibition of breast cancer metastasis by selective synthetic polypeptide against CXCR4. Cancer Research, 64(12), 4302–4308. https://doi.org/10.1158/0008-5472.CAN-03-3958.CrossRefPubMed

157.

Liang, Z., Yoon, Y., Votaw, J., Goodman, M. M., Williams, L., & Shim, H. (2005). Silencing of CXCR4 blocks breast cancer metastasis. Cancer Research, 65(3), 967–971.PubMedPubMedCentral

158.

Sun, Y.-X., Schneider, A., Jung, Y., Wang, J., Dai, J., Wang, J., et al. (2005). Skeletal localization and neutralization of the SDF-1(CXCL12)/CXCR4 axis blocks prostate cancer metastasis and growth in osseous sites in vivo. Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research, 20(2), 318–329. https://doi.org/10.1359/JBMR.041109.CrossRef

159.

Shahnazari, M., Chu, V., Wronski, T. J., Nissenson, R. A., & Halloran, B. P. (2013). CXCL12/CXCR4 signaling in the osteoblast regulates the mesenchymal stem cell and osteoclast lineage populations. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 27(9), 3505–3513. https://doi.org/10.1096/fj.12-225763.CrossRef

160.

Salcedo, R., & Oppenheim, J. J. (2003). Role of chemokines in angiogenesis: CXCL12/SDF-1 and CXCR4 interaction, a key regulator of endothelial cell responses. Microcirculation (New York, N.Y.: 1994), 10(3–4), 359–370. https://doi.org/10.1038/sj.mn.7800200.CrossRef

161.

Ma, J., Sun, X., Wang, Y., Chen, B., Qian, L., & Wang, Y. (2019). Fibroblast-derived CXCL12 regulates PTEN expression and is associated with the proliferation and invasion of colon cancer cells via PI3k/Akt signaling. Cell Communication and Signaling: CCS, 17. https://doi.org/10.1186/s12964-019-0432-5.

162.

Havens, A. M., Jung, Y., Sun, Y. X., Wang, J., Shah, R. B., Bühring, H. J., et al. (2006). The role of sialomucin CD164 (MGC-24v or endolyn) in prostate cancer metastasis. BMC Cancer, 6, 195. https://doi.org/10.1186/1471-2407-6-195.CrossRefPubMedPubMedCentral

163.

Dehghani, M., Kianpour, S., Zangeneh, A., & Mostafavi-Pour, Z. (2014). CXCL12 modulates prostate cancer cell adhesion by altering the levels or activities of β1-containing integrins. International Journal of Cell Biology. Research Article, Hindawi. https://doi.org/10.1155/2014/981750.

164.

Sehgal, G., Hua, J., Bernhard, E. J., Sehgal, I., Thompson, T. C., & Muschel, R. J. (1998). Requirement for matrix metalloproteinase-9 (gelatinase B) expression in metastasis by murine prostate carcinoma. The American Journal of Pathology, 152(2), 591–596.PubMedPubMedCentral

165.

Zhang, X. H.-F., Wang, Q., Gerald, W., Hudis, C. A., Norton, L., Smid, M., et al. (2009). Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell, 16(1), 67–78. https://doi.org/10.1016/j.ccr.2009.05.017.CrossRefPubMedPubMedCentral

166.

Shiozawa, Y., Pedersen, E. A., Havens, A. M., Jung, Y., Mishra, A., Joseph, J., et al. (2011). Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. The Journal of Clinical Investigation, 121(4), 1298–1312. https://doi.org/10.1172/JCI43414.CrossRefPubMedPubMedCentral

167.

Jung, Y., Wang, J., Lee, E., McGee, S., Berry, J. E., Yumoto, K., et al. (2015). Annexin 2–CXCL12 interactions regulate metastatic cell targeting and growth in the bone marrow. Molecular Cancer Research, 13(1), 197–207. https://doi.org/10.1158/1541-7786.MCR-14-0118.CrossRefPubMed

168.

Chinni, S. R., Yamamoto, H., Dong, Z., Sabbota, A., Bonfil, R. D., & Cher, M. L. (2008). CXCL12/CXCR4 transactivates HER2 in lipid rafts of prostate cancer cells and promotes growth of metastatic deposits in bone. Molecular cancer research: MCR, 6(3), 446–457. https://doi.org/10.1158/1541-7786.MCR-07-0117.CrossRefPubMed

169.

Conley-LaComb, M. K., Semaan, L., Singareddy, R., Li, Y., Heath, E. I., Kim, S., et al. (2016). Pharmacological targeting of CXCL12/CXCR4 signaling in prostate cancer bone metastasis. Molecular Cancer, 15. https://doi.org/10.1186/s12943-016-0552-0.

170.

Ardura, J. A., Gutiérrez-Rojas, I., Álvarez-Carrión, L., Rodríguez-Ramos, M. R., Pozuelo, J. M., & Alonso, V. (2019). The secreted matrix protein mindin increases prostate tumor progression and tumor-bone crosstalk via ERK 1/2 regulation. Carcinogenesis, 40(7), 828–839. https://doi.org/10.1093/carcin/bgz105.CrossRefPubMed

171.

Bellahcène, A., Bachelier, R., Detry, C., Lidereau, R., Clézardin, P., & Castronovo, V. (2007). Transcriptome analysis reveals an osteoblast-like phenotype for human osteotropic breast cancer cells. Breast Cancer Research and Treatment, 101(2), 135–148. https://doi.org/10.1007/s10549-006-9279-8.CrossRefPubMed

172.

Knerr, K., Ackermann, K., Neidhart, T., & Pyerin, W. (2004). Bone metastasis: Osteoblasts affect growth and adhesion regulons in prostate tumor cells and provoke osteomimicry. International Journal of Cancer, 111(1), 152–159. https://doi.org/10.1002/ijc.20223.CrossRefPubMed

173.

Lamoureux, F., Ory, B., Battaglia, S., Pilet, P., Heymann, M.-F., Gouin, F., et al. (2008). Relevance of a new rat model of osteoblastic metastases from prostate carcinoma for preclinical studies using zoledronic acid. International Journal of Cancer, 122(4), 751–760. https://doi.org/10.1002/ijc.23187.CrossRefPubMed

174.

Kim, M. S., Day, C. J., & Morrison, N. A. (2005). MCP-1 is induced by receptor activator of nuclear factor-{kappa}B ligand, promotes human osteoclast fusion, and rescues granulocyte macrophage colony-stimulating factor suppression of osteoclast formation. The Journal of Biological Chemistry, 280(16), 16163–16169. https://doi.org/10.1074/jbc.M412713200.CrossRefPubMed

175.

Ma, R.-Y., Zhang, H., Li, X.-F., Zhang, C.-B., Selli, C., Tagliavini, G., et al. (2020). Monocyte-derived macrophages promote breast cancer bone metastasis outgrowth. The Journal of Experimental Medicine, 217(11). https://doi.org/10.1084/jem.20191820.

176.

Siddiqui, J. A., & Partridge, N. C. (2017). CCL2/monocyte chemoattractant protein 1 and parathyroid hormone action on bone. Frontiers in Endocrinology, 8. https://doi.org/10.3389/fendo.2017.00049.

177.

Sul, O.-J., Ke, K., Kim, W.-K., Kim, S.-H., Lee, S.-C., Kim, H.-J., et al. (2012). Absence of MCP-1 leads to elevated bone mass via impaired actin ring formation. Journal of Cellular Physiology, 227(4), 1619–1627. https://doi.org/10.1002/jcp.22879.CrossRefPubMed

178.

Chiechi, A., Waning, D. L., Stayrook, K. R., Buijs, J. T., Guise, T. A., & Mohammad, K. S. (2013). Role of TGF-β in breast cancer bone metastases. Advances in bioscience and biotechnology (Print), 4(10C), 15–30. https://doi.org/10.4236/abb.2013.410A4003.CrossRef

179.

Guise, T. A., Yoneda, T., Yates, A. J., & Mundy, G. R. (1993). The combined effect of tumor-produced parathyroid hormone-related protein and transforming growth factor-alpha enhance hypercalcemia in vivo and bone resorption in vitro. The Journal of Clinical Endocrinology and Metabolism, 77(1), 40–45. https://doi.org/10.1210/jcem.77.1.8325957.CrossRefPubMed

180.

Qian, D. Z., Rademacher, B. L. S., Pittsenbarger, J., Huang, C.-Y., Myrthue, A., Higano, C. S., et al. (2010). CCL2 is induced by chemotherapy and protects prostate cancer cells from docetaxel - induced cytotoxicity. The Prostate, 70(4), 433–442. https://doi.org/10.1002/pros.21077.CrossRefPubMedPubMedCentral

181.

Liao, T. S., Yurgelun, M. B., Chang, S.-S., Zhang, H.-Z., Murakami, K., Blaine, T. A., et al. (2005). Recruitment of osteoclast precursors by stromal cell derived factor-1 (SDF-1) in giant cell tumor of bone. Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society, 23(1), 203–209. https://doi.org/10.1016/j.orthres.2004.06.018.CrossRef

182.

Zannettino, A. C. W., Farrugia, A. N., Kortesidis, A., Manavis, J., To, L. B., Martin, S. K., et al. (2005). Elevated serum levels of stromal-derived factor-1alpha are associated with increased osteoclast activity and osteolytic bone disease in multiple myeloma patients. Cancer Research, 65(5), 1700–1709. https://doi.org/10.1158/0008-5472.CAN-04-1687.CrossRefPubMed

183.

Fridlender, Z. G., Kapoor, V., Buchlis, G., Cheng, G., Sun, J., Wang, L.-C. S., et al. (2011). Monocyte chemoattractant protein–1 blockade inhibits lung cancer tumor growth by altering macrophage phenotype and activating CD8+ cells. American Journal of Respiratory Cell and Molecular Biology, 44(2), 230–237. https://doi.org/10.1165/rcmb.2010-0080OC.CrossRefPubMed

184.

Lu, Y., Chen, Q., Corey, E., Xie, W., Fan, J., Mizokami, A., & Zhang, J. (2009). Activation of MCP-1/CCR2 axis promotes prostate cancer growth in bone. Clinical & Experimental Metastasis, 26(2), 161–169. https://doi.org/10.1007/s10585-008-9226-7.CrossRef

185.

Roblek, M., Strutzmann, E., Zankl, C., Adage, T., Heikenwalder, M., Atlic, A., et al. (2016). Targeting of CCL2-CCR2-glycosaminoglycan axis using a CCL2 decoy protein attenuates metastasis through inhibition of tumor cell seeding. Neoplasia, 18(1), 49–59. https://doi.org/10.1016/j.neo.2015.11.013.CrossRefPubMedPubMedCentral

186.

Bertolini, F., Dell’Agnola, C., Mancuso, P., Rabascio, C., Burlini, A., Monestiroli, S., et al. (2002). CXCR4 neutralization, a novel therapeutic approach for non-Hodgkin’s lymphoma. Cancer Research, 62(11), 3106–3112.PubMed

187.

Brennecke, P., Arlt, M. J. E., Campanile, C., Husmann, K., Gvozdenovic, A., Apuzzo, T., et al. (2014). CXCR4 antibody treatment suppresses metastatic spread to the lung of intratibial human osteosarcoma xenografts in mice. Clinical & Experimental Metastasis, 31(3), 339–349. https://doi.org/10.1007/s10585-013-9632-3.CrossRef

188.

Gelmini, S., Mangoni, M., Castiglione, F., Beltrami, C., Pieralli, A., Andersson, K. L., et al. (2009). The CXCR4/CXCL12 axis in endometrial cancer. Clinical & Experimental Metastasis, 26(3), 261–268. https://doi.org/10.1007/s10585-009-9240-4.CrossRef

189.

Miura, K., Uniyal, S., Leabu, M., Oravecz, T., Chakrabarti, S., Morris, V. L., & Chan, B. M. C. (2005). Chemokine receptor CXCR4-beta1 integrin axis mediates tumorigenesis of osteosarcoma HOS cells. Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire, 83(1), 36–48. https://doi.org/10.1139/o04-106.CrossRefPubMed

190.

Murakami, T., Maki, W., Cardones, A. R., Fang, H., Tun Kyi, A., Nestle, F. O., & Hwang, S. T. (2002). Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells. Cancer Research, 62(24), 7328–7334.PubMed

191.

Tavor, S., Petit, I., Porozov, S., Avigdor, A., Dar, A., Leider-Trejo, L., et al. (2004). CXCR4 regulates migration and development of human acute myelogenous leukemia stem cells in transplanted NOD/SCID mice. Cancer Research, 64(8), 2817–2824. https://doi.org/10.1158/0008-5472.can-03-3693.CrossRefPubMed

192.

Zeelenberg, I. S., Ruuls-Van Stalle, L., & Roos, E. (2003). The chemokine receptor CXCR4 is required for outgrowth of colon carcinoma micrometastases. Cancer Research, 63(13), 3833–3839.PubMed

193.

Chen, Y., Stamatoyannopoulos, G., & Song, C.-Z. (2003). Down-regulation of CXCR4 by inducible small interfering RNA inhibits breast cancer cell invasion in vitro. Cancer Research, 63(16), 4801–4804.PubMed

194.

Brana, I., Calles, A., LoRusso, P. M., Yee, L. K., Puchalski, T. A., Seetharam, S., et al. (2015). Carlumab, an anti-C-C chemokine ligand 2 monoclonal antibody, in combination with four chemotherapy regimens for the treatment of patients with solid tumors: an open-label, multicenter phase 1b study. Targeted Oncology, 10(1), 111–123. https://doi.org/10.1007/s11523-014-0320-2.CrossRefPubMed

195.

Kuhne, M. R., Mulvey, T., Belanger, B., Chen, S., Pan, C., Chong, C., et al. (2013). BMS-936564/MDX-1338: a fully human anti-CXCR4 antibody induces apoptosis in vitro and shows antitumor activity in vivo in hematologic malignancies. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 19(2), 357–366. https://doi.org/10.1158/1078-0432.CCR-12-2333.CrossRef

196.

Pienta, K. J., Machiels, J.-P., Schrijvers, D., Alekseev, B., Shkolnik, M., Crabb, S. J., et al. (2013). Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer. Investigational New Drugs, 31(3), 760–768. https://doi.org/10.1007/s10637-012-9869-8.CrossRefPubMed

197.

Sandhu, S. K., Papadopoulos, K., Fong, P. C., Patnaik, A., Messiou, C., Olmos, D., et al. (2013). A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors. Cancer Chemotherapy and Pharmacology, 71(4), 1041–1050. https://doi.org/10.1007/s00280-013-2099-8.CrossRefPubMed

198.

Vergunst, C. E., Gerlag, D. M., Lopatinskaya, L., Klareskog, L., Smith, M. D., van den Bosch, F., et al. (2008). Modulation of CCR2 in rheumatoid arthritis: A double-blind, randomized, placebo-controlled clinical trial. Arthritis and Rheumatism, 58(7), 1931–1939. https://doi.org/10.1002/art.23591.CrossRefPubMed

199.

Pernas, S., Martin, M., Kaufman, P. A., Gil-Martin, M., Gomez Pardo, P., Lopez-Tarruella, S., et al. (2018). Balixafortide plus eribulin in HER2-negative metastatic breast cancer: A phase 1, single-arm, dose-escalation trial. The Lancet. Oncology, 19(6), 812–824. https://doi.org/10.1016/S1470-2045(18)30147-5.CrossRefPubMed

200.

Rajagopal, S., Bassoni, D. L., Campbell, J. J., Gerard, N. P., Gerard, C., & Wehrman, T. S. (2013). Biased agonism as a mechanism for differential signaling by chemokine receptors *. Journal of Biological Chemistry, 288(49), 35039–35048. https://doi.org/10.1074/jbc.M113.479113.CrossRef

201.

Salanga, C. L., O’Hayre, M., & Handel, T. (2009). Modulation of chemokine receptor activity through dimerization and crosstalk. Cellular and Molecular Life Sciences: CMLS, 66(8), 1370–1386. https://doi.org/10.1007/s00018-008-8666-1.CrossRefPubMed

202.

Schall, T. J., & Proudfoot, A. E. I. (2011). Overcoming hurdles in developing successful drugs targeting chemokine receptors. Nature Reviews Immunology, 11(5), 355–363. https://doi.org/10.1038/nri2972.CrossRefPubMed

203.

Stephens, B., & Handel, T. M. (2013). Chemokine receptor oligomerization and allostery. Progress in Molecular Biology and Translational Science, 115, 375–420. https://doi.org/10.1016/B978-0-12-394587-7.00009-9.CrossRefPubMedPubMedCentral

204.

Bégin-Lavallée, V., Midavaine, É., Dansereau, M.-A., Tétreault, P., Longpré, J.-M., Jacobi, A. M., et al. (2016). Functional inhibition of chemokine receptor CCR2 by dicer-substrate-siRNA prevents pain development. Molecular Pain, 12. https://doi.org/10.1177/1744806916653969.

205.

Collingwood, M. A., Rose, S. D., Hsuang, L., Hillier, C., Amarzguioui, M., Wiiger, M. T., et al. (2008). Chemical modification patterns compatible with high potency dicer-substrate small interfering RNAs. Oligonucleotides, 18(2), 187–199. https://doi.org/10.1089/oli.2008.0123.CrossRefPubMedPubMedCentral

206.

Brouillette, R. L., Besserer-Offroy, É., Mona, C. E., Chartier, M., Lavenus, S., Sousbie, M., et al. (2020). Cell-penetrating pepducins targeting the neurotensin receptor type 1 relieve pain. Pharmacological Research, 155, 104750. https://doi.org/10.1016/j.phrs.2020.104750.CrossRefPubMed

207.

Zhang, P., Covic, L., & Kuliopulos, A. (2015). Pepducins and other lipidated peptides as mechanistic probes and therapeutics. Methods in Molecular Biology (Clifton, N.J.), 1324, 191–203. https://doi.org/10.1007/978-1-4939-2806-4_13.CrossRef

Titel: The multifaceted roles of the chemokines CCL2 and CXCL12 in osteophilic metastatic cancers
verfasst von: Élora Midavaine
Jérôme Côté
Philippe Sarret
Publikationsdatum: 11.05.2021
Verlag: Springer US
Erschienen in: Cancer and Metastasis Reviews / Ausgabe 2/2021
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-021-09974-2

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

The multifaceted roles of the chemokines CCL2 and CXCL12 in osteophilic metastatic cancers

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Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

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