The role of fibroblast activation protein in health and malignancy

1.

Aoyama, A., & Chen, W. T. (1990). A 170-kDa membrane-bound protease is associated with the expression of invasiveness by human malignant melanoma cells. Proc Natl Acad Sci U S A, 87, 8296–8300.CrossRef

2.

Monsky, W. L., Lin, C. Y., Aoyama, A., Kelly, T., Akiyama, S. K., Mueller, S. C., & Chen, W. T. (1994). A potential marker protease of invasiveness, seprase, is localized on invadopodia of human malignant melanoma cells. Cancer Res, 54, 5702–5710.PubMed

3.

Piñeiro-Sánchez, M. L., Goldstein, L. A., Dodt, J., et al. (1997). Identification of the 170-kDa melanoma membrane-bound gelatinase (seprase) as a serine integral membrane protease. J Biol Chem, 272, 7595–7601. https://doi.org/10.1074/JBC.272.12.7595.CrossRefPubMed

4.

Mathew, S., Scanlan, M.J., Mohan Raj, B.K., et al (1995) The gene for fibroblast activation protein α (FAP), a putative cell surface-bound serine protease expressed in cancer stroma and wound healing, maps to chromosome band 2q23. Genomics 25:335–337. https://doi.org/10.1016/0888-7543(95)80157-H

5.

Iwasa, S., Jin, X., Okada, K., et al (2003) Increased expression of seprase, a membrane-type serine protease, is associated with lymph node metastasis in human colorectal cancer. Cancer Lett 199:91–98. https://doi.org/10.1016/S0304-3835(03)00315-X

6.

Kelly, T., Kechelava, S., Rozypal, T. L., et al. (1998). Seprase, a membrane-bound protease, is overexpressed by invasive ductal carcinoma cells of human breast cancers. Mod Pathol, 11, 855–863.PubMed

7.

Mori, Y., Kono, K., Matsumoto, Y., et al. (2004). The expression of a type II transmembrane serine protease (Seprase) in human gastric carcinoma. Oncology, 67, 411–419. https://doi.org/10.1159/000082926.CrossRefPubMed

8.

Lo, A., Li, C.-P., Buza, E. L., et al. (2017). Fibroblast activation protein augments progression and metastasis of pancreatic ductal adenocarcinoma. J Clin Invest, 2.

9.

Arnold, J. N., Magiera, L., Kraman, M., & Fearon, D. T. (2014). Tumoral immune suppression by macrophages expressing fibroblast activation protein-α and heme oxygenase-1. Cancer Immunol Res, 2, 121–126. https://doi.org/10.1158/2326-6066.CIR-13-0150.CrossRefPubMedPubMedCentral

10.

Lee, K. N., Jackson, K. W., Christiansen, V. J., et al. (2006). Antiplasmin-cleaving enzyme is a soluble form of fibroblast activation protein. Blood, 107, 1397–1404. https://doi.org/10.1182/blood-2005-08-3452.CrossRefPubMed

11.

Goldstein, L. A., Ghersi, G., Pineiro-Sanchez, M. L., et al. (1997). Molecular cloning of seprase: a serine integral membrane protease from human melanoma. Biochim Biophys Acta, 1361, 11–19.CrossRef

12.

Rosenblum, J.S., Kozarich, J.W. (2003) Prolyl peptidases: A serine protease subfamily with high potential for drug discovery. Curr Opin Chem Biol 7:496–504. https://doi.org/10.1016/S1367-5931(03)00084-X

13.

Collins, P. J., McMahon, G., O’Brien, P., & O’Connor, B. (2004). Purification, identification and characterisation of seprase from bovine serum. Int J Biochem Cell Biol, 36, 2320–2333. https://doi.org/10.1016/J.BIOCEL.2004.05.006.CrossRefPubMed

14.

Edosada, C. Y., Quan, C., Tran, T., et al. (2006). Peptide substrate profiling defines fibroblast activation protein as an endopeptidase of strict Gly ₂ -Pro ₁ -cleaving specificity. FEBS Lett, 580, 1581–1586. https://doi.org/10.1016/j.febslet.2006.01.087.CrossRefPubMed

15.

Aggarwal, S., Brennen, W. N., Kole, T. P., Schneider, E., Topaloglu, O., Yates, M., Cotter, R. J., & Denmeade, S. R. (2008). Fibroblast activation protein peptide substrates identified from human collagen I derived gelatin cleavage sites. Biochemistry, 47, 1076–1086. https://doi.org/10.1021/bi701921b.CrossRefPubMed

16.

Huang, C.-H., Suen, C.-S., Lin, C.-T., et al. (2011). Cleavage-site specificity of prolyl endopeptidase FAP investigated with a full-length protein substrate. J Biochem, 149, 685–692. https://doi.org/10.1093/jb/mvr017.CrossRefPubMed

17.

Keane, F. M., Nadvi, N. A., Yao, T.-W., & Gorrell, M. D. (2011). Neuropeptide Y, B-type natriuretic peptide, substance P and peptide YY are novel substrates of fibroblast activation protein-α. FEBS J, 278, 1316–1332. https://doi.org/10.1111/j.1742-4658.2011.08051.x.CrossRefPubMed

18.

Christiansen, V. J., Jackson, K. W., Lee, K. N., & McKee, P. A. (2007). Effect of fibroblast activation protein and alpha2-antiplasmin cleaving enzyme on collagen types I, III, and IV. Arch Biochem Biophys, 457, 177–186. https://doi.org/10.1016/j.abb.2006.11.006.CrossRefPubMed

19.

Levy, M. T., McCaughan, G. W., Abbott, C. A., Park, J. E., Cunningham, A. M., Müller, E., Rettig, W. J., & Gorrell, M. D. (1999). Fibroblast activation protein: A cell surface dipeptidyl peptidase and gelatinase expressed by stellate cells at the tissue remodelling interface in human cirrhosis. Hepatology, 29, 1768–1778. https://doi.org/10.1002/hep.510290631.CrossRefPubMed

20.

Dunshee, D. R., Bainbridge, T. W., Kljavin, N. M., et al. (2016). Fibroblast activation protein cleaves and inactivates fibroblast growth factor 21. J Biol Chem, 291, 5986–5996. https://doi.org/10.1074/jbc.M115.710582.CrossRefPubMedPubMedCentral

21.

Lee, K. N., Jackson, K. W., Christiansen, V. J., et al. (2004). A novel plasma proteinase potentiates alpha2-antiplasmin inhibition of fibrin digestion. Blood, 103, 3783–3788. https://doi.org/10.1182/blood-2003-12-4240.CrossRefPubMed

22.

Ramirez-Montagut, T., Blachere, N.E., Sviderskaya, E. V, et al (2004) FAPα, a surface peptidase expressed during wound healing, is a tumor suppressor. Oncogene 23:5435–5446. https://doi.org/10.1038/sj.onc.1207730

23.

Huang, Y., Simms, A. E., Mazur, A., et al. (2011). Fibroblast activation protein-α promotes tumor growth and invasion of breast cancer cells through non-enzymatic functions. Clin Exp Metastasis, 28, 567–579. https://doi.org/10.1007/s10585-011-9392-x.CrossRefPubMed

24.

Lv, B., Xie, F., Zhao, P., et al. (2016). Promotion of cellular growth and motility is independent of enzymatic activity of fibroblast activation protein-α. Cancer Genomics Proteomics, 13, 201–208.PubMed

25.

Aertgeerts, K., Levin, I., Shi, L., et al. (2005). Structural and kinetic analysis of the substrate specificity of human fibroblast activation protein alpha. J Biol Chem, 280, 19441–19444. https://doi.org/10.1074/jbc.C500092200.CrossRefPubMed

26.

Meadows, S. A., Edosada, C. Y., Mayeda, M., et al. (2007). Ala657 and conserved active site residues promote fibroblast activation protein endopeptidase activity via distinct mechanisms of transition state stabilization. Biochemistry, 46, 4598–4605. https://doi.org/10.1021/BI062227Y.CrossRefPubMed

27.

Sun, S., Albright, C. F., Fish, B. H., et al. (2002). Expression, purification, and kinetic characterization of full-length human fibroblast activation protein. Protein Expr Purif, 24, 274–281. https://doi.org/10.1006/PREP.2001.1572.CrossRefPubMed

28.

Ghersi, G., Zhao, Q., Salamone, M., et al. (2006). The protease complex consisting of dipeptidyl peptidase IV and seprase plays a role in the migration and invasion of human endothelial cells in collagenous matrices. Cancer Res, 66, 4652–4661. https://doi.org/10.1158/0008-5472.CAN-05-1245.CrossRefPubMedPubMedCentral

29.

Mueller, S. C., Ghersi, G., Akiyama, S. K., et al. (1999). A novel protease-docking function of integrin at invadopodia. J Biol Chem, 274, 24947–24952. https://doi.org/10.1074/JBC.274.35.24947.CrossRefPubMed

30.

Artym, V. V, Kindzelskii, A.L., Chen, W.-T., Petty, H.R. (2002) Molecular proximity of seprase and the urokinase-type plasminogen activator receptor on malignant melanoma cell membranes: dependence on beta1 integrins and the cytoskeleton. Carcinogenesis 23:1593–1601

31.

Cheng, J. D., Dunbrack, R. L., Valianou, M., et al. (2002). Promotion of tumor growth by murine fibroblast activation protein, a serine protease, in an animal model. CANCER Res, 62, 4767–4772.PubMed

32.

Niedermeyer, J., Enenkel, B., Park, J. E., et al. (1998). Mouse fibroblast-activation protein. Conserved Fap gene organization and biochemical function as a serine protease. Eur J Biochem, 254, 650–654. https://doi.org/10.1046/j.1432-1327.1998.2540650.x.CrossRefPubMed

33.

Brown, D. D., Wang, Z., Furlow, J. D., et al. (1996). The thyroid hormone-induced tail resorption program during Xenopus laevis metamorphosis. Dev Biol, 93, 1924–1929.

34.

Zhang, J., Valianou, M., & Cheng, J. D. (2010). Identification and characterization of the promoter of fibroblast activation protein. Front Biosci, 1154–1163.

35.

Goldstein, L. A., & Chen, W. T. (2000). Identification of an alternatively spliced seprase mRNA that encodes a novel intracellular isoform. J Biol Chem, 275, 2554–2559. https://doi.org/10.1074/JBC.275.4.2554.CrossRefPubMed

36.

Niedermeyer, J., Scanlan, M.J., Garin-Chesa, P., et al (1997) Mouse fibroblast activation protein: Molecular cloning, alternative splicing and expression in the reactive stroma of epithelial cancers. Int J Cancer 71:383–389. https://doi.org/10.1002/(SICI)1097-0215(19970502)71:3<383::AID-IJC14>3.0.CO;2-H

37.

Rettig, W. J., Su, S. L., Fortunato, S. R., et al. (1994). Fibroblast activation protein: Purification, epitope mapping and induction by growth factors. Int J Cancer, 58, 385–392. https://doi.org/10.1002/ijc.2910580314.CrossRefPubMed

38.

Chen, H., Yang, W.-W., Wen, Q.-T., et al. (2009). TGF-β-induced fibroblast activation protein expression, fibroblast activation protein expression increases the proliferation, adhesion, and migration of HO-8910 PM. Exp Mol Pathol, 87, 189–194. https://doi.org/10.1016/J.YEXMP.2009.09.001.CrossRefPubMed

39.

Wäster, P., Rosdahl, I., Gilmore, B. F., & Seifert, O. (2011). Ultraviolet exposure of melanoma cells induces fibroblast activation protein-α in fibroblasts: Implications for melanoma invasion. Faculty of Medicine, Laboratory of Clinical Virology: University of Crete.

40.

Kennedy, A., Dong, H., Chen, D., & Chen, W.-T. (2009). Elevation of seprase expression and promotion of an invasive phenotype by collagenous matrices in ovarian tumor cells. Int J Cancer, 124, 27–35. https://doi.org/10.1002/ijc.23871.CrossRefPubMedPubMedCentral

41.

LAI, D., MA, L., & WANG, F. (2012). Fibroblast activation protein regulates tumor-associated fibroblasts and epithelial ovarian cancer cells. Int J Oncol, 41, 541–550. https://doi.org/10.3892/ijo.2012.1475.CrossRefPubMed

42.

Ruan, P., Tao, Z., & Tan, A. (2018). Low expression of miR-30a-5p induced the proliferation and invasion of oral cancer via promoting the expression of FAP. Biosci Rep, 38, BSR20171027. https://doi.org/10.1042/BSR20171027.CrossRefPubMedPubMedCentral

43.

Kanamori, A., & Brown, D. D. (1996). The analysis of complex developmental programmes: Amphibian metamorphosis. Genes to Cells, 1, 429–435. https://doi.org/10.1046/j.1365-2443.1996.d01-251.x.CrossRefPubMed

44.

Niedermeyer, J., Kriz, M., Hilberg, F., et al. (2000). Targeted disruption of mouse fibroblast activation protein. Mol Cell Biol, 20, 1089–1094. https://doi.org/10.1128/MCB.20.3.1089-1094.2000.CrossRefPubMedPubMedCentral

45.

Niedermeyer, J., Garin-Chesa, P., Kriz, M., et al. (2001). Expression of the fibroblast activation protein during mouse embryo development. Int J Dev Biol, 45, 445–447. https://doi.org/10.1387/IJDB.11330865.CrossRefPubMed

46.

Roberts, E. W., Deonarine, A., Jones, J. O., et al. (2013). Depletion of stromal cells expressing fibroblast activation protein-α from skeletal muscle and bone marrow results in cachexia and anemia. J Exp Med, 210, 1137–1151. https://doi.org/10.1084/jem.20122344.CrossRefPubMedPubMedCentral

47.

Keane, F. M., Yao, T.-W., Seelk, S., et al. (2014). Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs. FEBS Open Bio, 4, 43–54. https://doi.org/10.1016/j.fob.2013.12.001.CrossRef

48.

Garin-Chesa, P., Oldt, L. J., & Rettigt, W. J. (1990). Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers. Immunology, 87, 7235–7239.

49.

Levy, M., McCaughan, G., Marinos, G., & Gorrell, M. (2002). Intrahepatic expression of the hepatic stellate cell marker fibroblast activation protein correlates with the degree of fibrosis in hepatitis C virus infection. Liver Int, 22, 93–101. https://doi.org/10.1034/j.1600-0676.2002.01503.x.CrossRef

50.

Uitte de Willige, S., Malfliet, J. J. M. C., Janssen, H. L. A., et al. (2013). Increased N-terminal cleavage of alpha-2-antiplasmin in patients with liver cirrhosis. J Thromb Haemost, 11, 2029–2036. https://doi.org/10.1111/jth.12396.CrossRefPubMed

51.

Uitte de Willige, S., Keane, F. M., Bowen, D. G., Malfliet, J. J. M. C., Zhang, H. E., Maneck, B., McCaughan, G. W., Leebeek, F. W. G., Rijken, D. C., & Gorrell, M. D. (2017). Circulating fibroblast activation protein activity and antigen levels correlate strongly when measured in liver disease and coronary heart disease. PLoS One, 12, e0178987. https://doi.org/10.1371/journal.pone.0178987.CrossRefPubMedPubMedCentral

52.

Williams, K. H., Viera de Ribeiro, A. J., Prakoso, E., et al. (2015). Lower serum fibroblast activation protein shows promise in the exclusion of clinically significant liver fibrosis due to non-alcoholic fatty liver disease in diabetes and obesity. Diabetes Res Clin Pract, 108, 466–472. https://doi.org/10.1016/J.DIABRES.2015.02.024.CrossRefPubMed

53.

Acharya, P. S., Zukas, A., Chandan, V., Katzenstein, A. L. A., & Puré, E. (2006). Fibroblast activation protein: a serine protease expressed at the remodeling interface in idiopathic pulmonary fibrosis. Hum Pathol, 37, 352–360.CrossRef

54.

Wenlong, L., Leilei, Y., Wei, F., et al. (2015). Luciferase expression is driven by the promoter of fibroblast activation protein-α in murine pulmonary fibrosis. Biotechnol Lett, 37, 1757–1763. https://doi.org/10.1007/s10529-015-1855-8.CrossRefPubMed

55.

Fan, M.-H., Zhu, Q., Li, H.-H., et al. (2016). Fibroblast activation protein (FAP) accelerates collagen degradation and clearance from lungs in mice. J Biol Chem, 291, 8070–8089. https://doi.org/10.1074/jbc.M115.701433.CrossRefPubMed

56.

Egger, C., Cannet, C., Gérard, C., et al. (2017). Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis. Eur J Pharmacol, 809, 64–72. https://doi.org/10.1016/j.ejphar.2017.05.022.CrossRefPubMed

57.

Dienus, K., Bayat, A., Gilmore, B. F., & Seifert, O. (2010). Increased expression of fibroblast activation protein-alpha in keloid fibroblasts: implications for development of a novel treatment option. Arch Dermatol Res, 302, 725–731. https://doi.org/10.1007/s00403-010-1084-x.CrossRefPubMed

58.

Rovedatti, L., Di Sabatino, A., Knowles, C. H., et al. (2011). Fibroblast activation protein expression in Crohnʼs disease strictures. Inflamm Bowel Dis, 17, 1251–1253. https://doi.org/10.1002/ibd.21446.CrossRefPubMed

59.

Scott, A. M., Wiseman, G., Welt, S., Adjei, A., Lee, F. T., Hopkins, W., Divgi, C. R., Hanson, L. H., Mitchell, P., Gansen, D. N., Larson, S. M., Ingle, J. N., Hoffman, E. W., Tanswell, P., Ritter, G., Cohen, L. S., Bette, P., Arvay, L., Amelsberg, A., Vlock, D., Rettig, W. J., & Old, L. J. (2003). A Phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer. Clin Cancer Res, 9, 1639–1647.PubMed

60.

Milner, J. M., Kevorkian, L., Young, D. A., et al. (2006). Fibroblast activation protein alpha is expressed by chondrocytes following a pro-inflammatory stimulus and is elevated in osteoarthritis. Arthritis Res Ther, 8, R23. https://doi.org/10.1186/ar1877.CrossRefPubMedPubMedCentral

61.

Bauer, S., Jendro, M. C., Wadle, A., et al. (2006). Fibroblast activation protein is expressed by rheumatoid myofibroblast-like synoviocytes. Arthritis Res Ther, 8. https://doi.org/10.1186/ar2080.

62.

Ospelt, C., Mertens, J. C., Jüngel, A., et al. (2010). Inhibition of fibroblast activation protein and dipeptidylpeptidase 4 increases cartilage invasion by rheumatoid arthritis synovial fibroblasts. Arthritis Rheum, 62, 1224–1235. https://doi.org/10.1002/art.27395.CrossRefPubMed

63.

Busso, N., Wagtmann, N., Herling, C., et al. (2005). Circulating CD26 is negatively associated with inflammation in human and experimental arthritis. Immunopathol Infect Dis, 166, 433–442.

64.

Wäldele, S., Koers-Wunrau, C., Beckmann, D., Korb-Pap, A., Wehmeyer, C., Pap, T., & Dankbar, B. (2015). Deficiency of fibroblast activation protein alpha ameliorates cartilage destruction in inflammatory destructive arthritis. Arthritis Res Ther, 17, 12. https://doi.org/10.1186/s13075-015-0524-6.CrossRefPubMedPubMedCentral

65.

Laverman, P., van der Geest, T., Terry, S. Y. A., et al. (2015). Immuno-PET and immuno-SPECT of rheumatoid arthritis with radiolabeled anti-fibroblast activation protein antibody correlates with severity of arthritis. J Nucl Med, 56, 778–783. https://doi.org/10.2967/jnumed.114.152959.CrossRefPubMed

66.

Brokopp, C. E., Schoenauer, R., Richards, P., et al. (2011). Fibroblast activation protein is induced by inflammation and degrades type I collagen in thin-cap fibroatheromata. Eur Heart J, 32, 2713–2722. https://doi.org/10.1093/eurheartj/ehq519.CrossRefPubMedPubMedCentral

67.

Tillmanns, J., Widera, C., Habbaba, Y., et al. (2013). Circulating concentrations of fibroblast activation protein α in apparently healthy individuals and patients with acute coronary syndrome as assessed by sandwich ELISA ☆. Int J Cardiol, 168, 3926–3931. https://doi.org/10.1016/j.ijcard.2013.06.061.CrossRefPubMed

68.

Uitte De Willige, S., Malfliet, J. J. M. C., Deckers, J. W., et al. (2015). Plasma levels of soluble fibroblast activation protein in arterial thrombosis; determinants and cleavage of its substrate alpha-2-antiplasmin ☆. Int J Cardiol, 178, 105–110. https://doi.org/10.1016/j.ijcard.2014.10.091.CrossRefPubMed

69.

Tillmanns, J., Hoffmann, D., Habbaba, Y., et al. (2015). Fibroblast activation protein alpha expression identifies activated fibroblasts after myocardial infarction. J Mol Cell Cardiol, 87, 194–203. https://doi.org/10.1016/J.YJMCC.2015.08.016.CrossRefPubMed

70.

Tillmanns, J., Fraccarollo, D., Galuppo, P., et al. (2017). Changes in concentrations of circulating fibroblast activation protein alpha are associated with myocardial damage in patients with acute ST-elevation MI. Int J Cardiol, 232, 155–159. https://doi.org/10.1016/j.ijcard.2017.01.037.CrossRefPubMed

71.

Zhen, E. Y., Jin, Z., Ackermann, B. L., et al. (2016). Circulating FGF21 proteolytic processing mediated by fibroblast activation protein. Biochem J, 473, 605–614. https://doi.org/10.1042/BJ20151085.CrossRefPubMedPubMedCentral

72.

Sánchez-Garrido, M. A., Habegger, K. M., Clemmensen, C., Holleman, C., Müller, T. D., Perez-Tilve, D., Li, P., Agrawal, A. S., Finan, B., Drucker, D. J., Tschöp, M. H., DiMarchi, R. D., & Kharitonenkov, A. (2016). Fibroblast activation protein (FAP) as a novel metabolic target. Mol Metab, 5, 1015–1024. https://doi.org/10.1016/j.molmet.2016.07.003.CrossRefPubMedPubMedCentral

73.

Hua, X., Yu, L., Huang, X., et al. (2011). Expression and role of fibroblast activation protein-alpha in microinvasive breast carcinoma. Diagn Pathol, 6, 111. https://doi.org/10.1186/1746-1596-6-111.CrossRefPubMedPubMedCentral

74.

Goodman, J. D., Rozypal, T. L., & Kelly, T. (2003). Seprase, a membrane-bound protease, alleviates the serum growth requirement of human breast cancer cells. Clin Exp Metastasis, 20, 459–470.CrossRef

75.

Park, C. K., Jung, W. H., & Koo, J. S. (2016). Expression of cancer-associated fibroblast-related proteins differs between invasive lobular carcinoma and invasive ductal carcinoma. Breast Cancer Res Treat, 159, 55–69. https://doi.org/10.1007/s10549-016-3929-2.CrossRefPubMed

76.

Park, S. Y., Kim, H. M., & Koo, J. S. (2015). Differential expression of cancer-associated fibroblast-related proteins according to molecular subtype and stromal histology in breast cancer. Breast Cancer Res Treat, 149, 727–741. https://doi.org/10.1007/s10549-015-3291-9.CrossRefPubMed

77.

Jung, Y. Y., Lee, Y. K., & Koo, J. S. (2015). Expression of cancer-associated fibroblast-related proteins in adipose stroma of breast cancer. Tumor Biol, 36, 8685–8695. https://doi.org/10.1007/s13277-015-3594-9.CrossRef

78.

Gong, C., Nie, Y., Qu, S., et al. (2014). Molecular and cellular pathobiology miR-21 induces myofibroblast differentiation and promotes the malignant progression of breast phyllodes tumors. Cancer Res, 74, 4341–4352. https://doi.org/10.1158/0008-5472.CAN-14-0125.CrossRefPubMed

79.

Yu, H., Yang, J., Li, Y., & Jiao, S. (2015). The expression of fibroblast activation protein-α in primary breast cancer is associated with poor prognosis. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 31, 370–374.PubMed

80.

Jia, J., Martin, T. A., Ye, L., & Jiang, W. G. (2014). FAP-α (fibroblast activation protein-α) is involved in the control of human breast cancer cell line growth and motility via the FAK pathway. BMC Cell Biol, 15, 16. https://doi.org/10.1186/1471-2121-15-16.CrossRefPubMedPubMedCentral

81.

Ariga, N., Sato, E., Ohuchi, N., et al. (2001). Stromal expression of fibroblast activation protein/seprase, a cell membrane serine proteinase and gelatinase, is associated with longer survival in patients with invasive ductal carcinoma of breast. Int J cancer, 95, 67–72.CrossRef

82.

Henry, L. R., Lee, H.-O., Lee, J. S., et al. (2007). Clinical implications of fibroblast activation protein in patients with colon cancer. Clin Cancer Res, 13, 1736–1741. https://doi.org/10.1158/1078-0432.CCR-06-1746.CrossRefPubMed

83.

Wikberg, M. L., Edin, S., Lundberg, I. V., Lundberg, I. V., van Guelpen, B., Dahlin, A. M., Rutegård, J., Stenling, R., Öberg, Å., & Palmqvist, R. (2013). High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis. Tumor Biol, 34, 1013–1020. https://doi.org/10.1007/s13277-012-0638-2.CrossRef

84.

Yang, X., Lin, Y., Shi, Y., Li, B., Liu, W., Yin, W., Dang, Y., Chu, Y., Fan, J., & He, R. (2016). FAP promotes immunosuppression by cancer-associated fibroblasts in the tumor microenvironment via STAT3-CCL2 signaling. Cancer Res, 76, 4124–4135. https://doi.org/10.1158/0008-5472.CAN-15-2973.CrossRefPubMed

85.

Shi, M., Yu, D.-H., Chen, Y., et al. (2012). Expression of fibroblast activation protein in human pancreatic adenocarcinoma and its clinicopathological significance. World J Gastroenterol, 18, 840–846. https://doi.org/10.3748/wjg.v18.i8.840.CrossRefPubMedPubMedCentral

86.

Cohen, S. J., Alpaugh, R. K., Palazzo, I., et al. (2008). Fibroblast activation protein and its relationship to clinical outcome in pancreatic adenocarcinoma. Pancreas, 37, 154–158. https://doi.org/10.1097/MPA.0b013e31816618ce.CrossRefPubMed

87.

Feig, C., Jones, J. O., Kraman, M., et al. (2013). Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci U S A, 110, 20212–20217. https://doi.org/10.1073/pnas.1320318110.CrossRefPubMedPubMedCentral

88.

Kawase, T., Yasui, Y., Nishina, S., et al. (2015). Fibroblast activation protein-α-expressing fibroblasts promote the progression of pancreatic ductal adenocarcinoma. BMC Gastroenterol, 15, 109. https://doi.org/10.1186/s12876-015-0340-0.CrossRefPubMedPubMedCentral

89.

Park, H., Lee, Y., Lee, H., et al. (2017). The prognostic significance of cancer-associated fibroblasts in pancreatic ductal adenocarcinoma. Tumor Biol 1–9. https://doi.org/10.1177/1010428317718403.

90.

Okada, K., Chen, W.-T., Iwasa, S., et al. (2003). Seprase, a membrane-type serine protease, has different expression patterns in intestinal- and diffuse-type gastric cancer. Oncology, 65, 363–370. https://doi.org/10.1159/000074650.CrossRefPubMed

91.

Hu, M., Qian, C., Hu, Z., et al. (2017). Biomarkers in tumor microenvironment? Upregulation of fibroblast activation protein-α correlates with gastric cancer progression and poor prognosis. Omi A J Integr Biol, 21, 38–44. https://doi.org/10.1089/omi.2016.0159.CrossRef

92.

Wen, X., He, X., Jiao, F., et al. (2017). Fibroblast activation protein-α-positive fibroblasts promote gastric cancer progression and resistance to immune checkpoint blockade. Oncol Res Featur Preclin Clin Cancer Ther, 25, 629–640. https://doi.org/10.3727/096504016X14768383625385.CrossRef

93.

Dong, R., Guo, J., Zhang, Z., Zhou, Y., & Hua, Y. (2018). Polyphyllin I inhibits gastric cancer cell proliferation by downregulating the expression of fibroblast activation protein alpha (FAP) and hepatocyte growth factor (HGF) in cancer-associated fibroblasts. Biochem Biophys Res Commun, 497, 1129–1134. https://doi.org/10.1016/j.bbrc.2018.02.193.CrossRefPubMed

94.

Rettig, W. J., Chesa, P. G., Beresford, H. R., et al. (1986). Differential expression of cell surface antigens and glial fibrillary acidic protein in human astrocytoma subsets. Cancer Res, 46, 6406–6412.PubMed

95.

Stremenova, J., Krepela, E., Mares, V., et al. (2007). Expression and enzymatic activity of dipeptidyl peptidase-IV in human astrocytic tumours are associated with tumour grade. Int J Oncol, 31, 785–792. https://doi.org/10.3892/ijo.31.4.785.CrossRefPubMed

96.

Mikheeva, S. A., Mikheev, A. M., Petit, A., et al. (2010). TWIST1 promotes invasion through mesenchymal change in human glioblastoma. Mol Cancer, 9, 194.CrossRef

97.

Matrasova, I., Busek, P., Balaziova, E., & Sedo, A. (2017). Heterogeneity of molecular forms of dipeptidyl peptidase-IV and fibroblast activation protein in human glioblastomas. Biomed Pap, 161, 252–260. https://doi.org/10.5507/bp.2017.010.CrossRef

98.

Mentlein, R., Hattermann, K., Hemion, C., et al. (2011). Expression and role of the cell surface protease seprase/fibroblast activation protein-a (FAP-a) in astroglial tumors. Biol Chem, 392, 199–207. https://doi.org/10.1515/BC.2010.119.CrossRefPubMed

99.

Busek, P., Balaziova, E., Matrasova, I., et al. (2016). Fibroblast activation protein alpha is expressed by transformed and stromal cells and is associated with mesenchymal features in glioblastoma. Tumor Biol, 37, 13961–13971. https://doi.org/10.1007/s13277-016-5274-9.CrossRef

100.

Zhang, Y., Tang, H., Cai, J., et al. (2011). Ovarian cancer-associated fibroblasts contribute to epithelial ovarian carcinoma metastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion. Cancer Lett, 303, 47–55. https://doi.org/10.1016/J.CANLET.2011.01.011.CrossRefPubMed

101.

Yang, L., Ma, L., & Lai, D. (2013). Over-expression of fibroblast activation protein alpha increases tumor growth in xenografts of ovarian cancer cells. Acta Biochim Biophys Sin, 45, 928–937. https://doi.org/10.1093/abbs/gmt095.CrossRefPubMed

102.

Zhang, M.-Z., Qiao, Y.-H., Nesland, J. M., et al. (2007). Expression of seprase in effusions from patients with epithelial ovarian carcinoma. Chin Med J (Engl), 120, 663–668.CrossRef

103.

Zhang, M., Xu, L., Wang, X., et al. (2015). Expression levels of seprase/FAPα and DPPIV/CD26 in epithelial ovarian carcinoma. Oncol Lett, 10, 34–42. https://doi.org/10.3892/ol.2015.3151.CrossRefPubMedPubMedCentral

104.

Ge, Y., Zhan, F., Barlogie, B., et al. (2006). Fibroblast activation protein (FAP) is upregulated in myelomatous bone and supports myeloma cell survival. Br J Haematol, 133, 83–92. https://doi.org/10.1111/j.1365-2141.2006.05976.x.CrossRefPubMed

105.

Pennisi, A., Li, X., Ling, W., Khan, S., Gaddy, D., Suva, L. J., Barlogie, B., Shaughnessy, J. D., Aziz, N., & Yaccoby, S. (2009). Inhibitor of DASH proteases affects expression of adhesion molecules in osteoclasts and reduces myeloma growth and bone disease. Br J Haematol, 145, 775–787. https://doi.org/10.1111/j.1365-2141.2009.07696.x.CrossRefPubMedPubMedCentral

106.

Huber, M. A., Schubert, R. D., Peter, R. U., Kraut, N., Park, J. E., Rettig, W. J., & Garin-Chesa, P. (2003). Fibroblast activation protein: Differential expression and serine protease activity in reactive stromal fibroblasts of melanocytic skin tumors. J Invest Dermatol, 120, 182–188. https://doi.org/10.1046/J.1523-1747.2003.12035.X.CrossRefPubMed

107.

Liu, F., Qi, L., Liu, B., et al. (2015). Fibroblast activation protein overexpression and clinical implications in solid tumors: A meta-analysis. PLoS One, 10, e0116683. https://doi.org/10.1371/journal.pone.0116683.CrossRefPubMedPubMedCentral

108.

Nakahara, H., Nomizu, M., Akiyama, S. K., et al. (1996). A mechanism for regulation of melanoma invasion. Ligation of alpha6beta1 integrin by laminin G peptides. J Biol Chem, 271, 27221–27224. https://doi.org/10.1074/JBC.271.44.27221.CrossRefPubMed

109.

Yang, W., Han, W., Ye, S., et al. (2013). Fibroblast activation protein-α promotes ovarian cancer cell proliferation and invasion via extracellular and intracellular signaling mechanisms. Exp Mol Pathol, 95, 105–110. https://doi.org/10.1016/j.yexmp.2013.06.007.CrossRefPubMed

110.

Lee, H.-O., Mullins, S. R., Franco-Barraza, J., Valianou, M., Cukierman, E., & Cheng, J. D. (2011). FAP-overexpressing fibroblasts produce an extracellular matrix that enhances invasive velocity and directionality of pancreatic cancer cells. BMC Cancer, 11, 245. https://doi.org/10.1186/1471-2407-11-245.CrossRefPubMedPubMedCentral

111.

Jia, J., Martin, T., Ye, L., et al. (2017). Fibroblast activation protein-α promotes the growth and migration of lung cancer cells via the PI3K and sonic hedgehog pathways. Int J Mol Med, 41, 275–283. https://doi.org/10.3892/ijmm.2017.3224.CrossRefPubMedPubMedCentral

112.

Wang, H., Wu, Q., Liu, Z., et al. (2014). Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma. Cell Death Dis, 122. https://doi.org/10.1038/cddis.2014.122.

113.

Aimes, R. T., Zijlstra, A., Hooper, J. D., et al. (2003). Endothelial cell serine proteases expressed during vascular morphogenesis and angiogenesis. Thromb Haemost, 89, 561–572.CrossRef

114.

Gao, L.-M., Wang, F., Zheng, Y., Fu, Z. Z., Zheng, L., & Chen, L. L. (2017). Roles of fibroblast activation protein and hepatocyte growth factor expressions in angiogenesis and metastasis of gastric cancer. Pathol Oncol Res, 25, 1–8. https://doi.org/10.1007/s12253-017-0359-3.CrossRef

115.

Santos, A. M., Jung, J., Aziz, N., Kissil, J. L., & Puré, E. (2009). Targeting fibroblast activation protein inhibits tumor stromagenesis and growth in mice. J Clin Invest, 119, 3613–3625. https://doi.org/10.1172/JCI38988.CrossRefPubMedPubMedCentral

116.

Christiansen, V. J., Jackson, K. W., Lee, K. N., et al. (2013). Targeting inhibition of fibroblast activation protein-α and prolyl oligopeptidase activities on cells common to metastatic tumor microenvironments. Neoplasia, 15, 348–358. https://doi.org/10.1593/NEO.121850.CrossRefPubMedPubMedCentral

117.

Bhati, R., Patterson, C., Livasy, C. A., et al. (2008). Molecular characterization of human breast tumor vascular cells. Am J Pathol, 172, 1381–1390. https://doi.org/10.2353/ajpath.2008.070988.CrossRefPubMedPubMedCentral

118.

Zukowska, Z., Grant, D.S., Lee, E.W. (2003) Neuropeptide Y: A novel mechanism for ischemic angiogenesis. Trends Cardiovasc Med 13:86–92. https://doi.org/10.1016/S1050-1738(02)00232-3

119.

Vu, T. H., Shipley, J. M., Bergers, G., et al. (1998). MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell, 93, 411–422.CrossRef

120.

Kahounová, Z., Kurfürstová, D., Bouchal, J., et al. (2017). The fibroblast surface markers FAP, anti-fibroblast, and FSP are expressed by cells of epithelial origin and may be altered during epithelial-to-mesenchymal transition. Cytom Part A. https://doi.org/10.1002/cyto.a.23101.

121.

Kraman, M., Bambrough, P. J., Arnold, J. N., et al. (2010). Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein. Science (80- ) 330:827–830. https://doi.org/10.1126/science.1195300.

122.

Chen, L., Qiu, X., Wang, X., & He, J. (2017). FAP positive fibroblasts induce immune checkpoint blockade resistance in colorectal cancer via promoting immunosuppression. Biochem Biophys Res Commun, 487, 8–14. https://doi.org/10.1016/j.bbrc.2017.03.039.CrossRefPubMed

123.

Sorrentino, C., Miele, L., Porta, A., Pinto, A., & Morello, S. (2016). Activation of the A2B adenosine receptor in B16 melanomas induces CXCL12 expression in FAP-positive tumor stromal cells, enhancing tumor progression. Oncotarget, 7, 64274–64288. https://doi.org/10.18632/oncotarget.11729.CrossRefPubMedPubMedCentral

124.

Kilvaer, T. K., Rakaee, M., Hellevik, T., et al. (2018). Tissue analyses reveal a potential immune-adjuvant function of FAP-1 positive fibroblasts in non-small cell lung cancer. PLoS One, 13, e0192157. https://doi.org/10.1371/journal.pone.0192157.CrossRefPubMedPubMedCentral

125.

Chung, K.-M., Hsu, S.-C., Chu, Y.-R., et al. (2014). Fibroblast activation protein (FAP) is essential for the migration of bone marrow mesenchymal stem cells through RhoA activation. PLoS One, 9, e88772. https://doi.org/10.1371/journal.pone.0088772.CrossRefPubMedPubMedCentral

126.

Yue, D., Li, H., Che, J., et al. (2014). Hedgehog/Gli promotes epithelial-mesenchymal transition in lung squamous cell carcinomas. J Exp Clin Cancer Res, 33, 34. https://doi.org/10.1186/1756-9966-33-34.CrossRefPubMedPubMedCentral

127.

Bailey, J. M., Swanson, B. J., Hamada, T., Eggers, J. P., Singh, P. K., Caffery, T., Ouellette, M. M., & Hollingsworth, M. A. (2008). Sonic hedgehog promotes desmoplasia in pancreatic cancer. Clin Cancer Res, 14, 5995–6004. https://doi.org/10.1158/1078-0432.CCR-08-0291.CrossRefPubMedPubMedCentral

128.

Walsh, M. P., Duncan, B., Larabee, S., et al. (2013). Val-BoroPro accelerates T Cell priming via modulation of dendritic cell trafficking resulting in complete regression of established murine tumors. PLoS One, 8. https://doi.org/10.1371/journal.pone.0058860.

129.

Adams, S., Miller, G. T., Jesson, M. I., et al. (2004). PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. CANCER Res, 64, 5471–5480.CrossRef

130.

Li, M., Li, M., Yin, T., et al. (2016). Targeting of cancer-associated fibroblasts enhances the efficacy of cancer chemotherapy by regulating the tumor microenvironment. Mol Med Rep, 13, 2476–2484. https://doi.org/10.3892/mmr.2016.4868.CrossRefPubMedPubMedCentral

131.

Okondo, M. C., Johnson, D. C., Sridharan, R., et al. (2017). DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol, 13, 46–53. https://doi.org/10.1038/nchembio.2229.CrossRefPubMed

132.

Meany, H., Balis, F. M., Aikin, A., Whitcomb, P., Murphy, R. F., Steinberg, S. M., Widemann, B. C., & Fox, E. (2010). Pediatric phase i trial design using maximum target inhibition as the primary endpoint. J Natl Cancer Inst, 102, 909–912. https://doi.org/10.1093/jnci/djq174.CrossRefPubMedPubMedCentral

133.

Eager, R. M., Cunningham, C. C., Senzer, N. N., et al. (2009). Phase II assessment of talabostat and cisplatin in second-line stage IV melanoma. BMC Cancer, 9, 263. https://doi.org/10.1186/1471-2407-9-263.CrossRefPubMedPubMedCentral

134.

Eager, R. M., Cunningham, C. C., Senzer, N., et al. (2009). Phase II trial of talabostat and docetaxel in advanced non-small cell lung cancer. Clin Oncol, 21, 464–472. https://doi.org/10.1016/J.CLON.2009.04.007.CrossRef

135.

Jones, B., Adams, S., Miller, G. T., et al. (2003). Hematopoietic stimulation by a dipeptidyl peptidase inhibitor reveals a novel regulatory mechanism and therapeutic treatment for blood cell deficiencies. Blood, 102, 1641–1648. https://doi.org/10.1182/blood-2003-01-0208.CrossRefPubMed

136.

Jansen, K., Heirbaut, L., Verkerk, R., et al. (2014). Extended structure−activity relationship and pharmacokinetic investigation of (4-Quinolinoyl)glycyl-2-cyanopyrrolidine inhibitors of fibroblast activation protein (FAP). J Med Chem, 57, 3053–3074. https://doi.org/10.1021/jm500031w.CrossRefPubMed

137.

Tanswell, P., Garin-Chesa, P., Rettig, W. J., Welt, S., Divgi, C. R., Casper, E. S., Finn, R. D., Larson, S. M., Old, L. J., & Scott, A. M. (2001). Population pharmacokinetics of antifibroblast activation protein monoclonal antibody F19 in cancer patients. Br J Clin Pharmacol, 51, 177–180. https://doi.org/10.1111/j.1365-2125.2001.01335.x.CrossRefPubMedPubMedCentral

138.

Welt, S., Divgi, C. R., Scott, A. M., et al. (1994). Antibody targeting in metastatic colon cancer: a phase I study of monoclonal antibody F19 against a cell-surface protein of reactive tumor stromal fibroblasts. J Clin Oncol, 12, 1193–1203. https://doi.org/10.1200/JCO.1994.12.6.1193.CrossRefPubMed

139.

Zhang, J., Valianou, M., Simmons, H., et al. (2013). Identification of inhibitory scFv antibodies targeting fibroblast activation protein utilizing phage display functional screens. FASEB J, 27, 581–589. https://doi.org/10.1096/fj.12-210377.CrossRefPubMedPubMedCentral

140.

Schmidt, A., Müller, D., Mersmann, M., Wüest, T., Gerlach, E., Garin-Chesa, P., Rettig, W. J., Pfizenmaier, K., & Moosmayer, D. (2001). Generation of human high-affinity antibodies specific for the fibroblast activation protein by guided selection. Eur J Biochem, 268, 1730–1738.CrossRef

141.

Wüest, T., Moosmayer, D., & Pfizenmaier, K. (2001). Construction of a bispecific single chain antibody for recruitment of cytotoxic T cells to the tumour stroma associated antigen fibroblast activation protein. J Biotechnol, 92, 159–168.CrossRef

142.

Hornig, N., Kermer, V., Frey, K., et al. (2012). Combination of a bispecific antibody and costimulatory antibody-ligand fusion proteins for targeted cancer immunotherapy. J Immunother, 35, 418–429. https://doi.org/10.1097/CJI.0b013e3182594387.CrossRefPubMed

143.

Hofheinz, R.-D., al-Batran, S.-E., Hartmann, F., et al (2003) Stromal antigen targeting by a humanised monoclonal antibody: An early phase II trial of sibrotuzumab in patients with metastatic colorectal cancer. Oncol Res Treat 26:44–48. https://doi.org/10.1159/000069863

144.

Fischer, E., Chaitanya, K., Wüest, T., et al. (2012). Radioimmunotherapy of fibroblast activation protein positive tumors by rapidly internalizing antibodies. Clin Cancer Res, 18, 6208–6218. https://doi.org/10.1158/1078-0432.CCR-12-0644.CrossRefPubMed

145.

Wang, J., Li, Q., Li, X., et al. (2017). A novel FAPα-based Z-Gly-Pro epirubicin prodrug for improving tumor- targeting chemotherapy. Eur J Pharmacol, 815, 166–172. https://doi.org/10.1016/j.ejphar.2017.09.016.CrossRefPubMed

146.

Huang, S., Zhang, Y., Zhong, J., et al. (2018). Toxicological profile and safety pharmacology of a single dose of fibroblast activation protein-α-based doxorubicin prodrug. Anticancer Drugs, 29, 1. https://doi.org/10.1097/CAD.0000000000000593.CrossRef

147.

Chen, M., Lei, X., Shi, C., Huang, M., Li, X., Wu, B., Li, Z., Han, W., du, B., Hu, J., Nie, Q., Mai, W., Ma, N., Xu, N., Zhang, X., Fan, C., Hong, A., Xia, M., Luo, L., Ma, A., Li, H., Yu, Q., Chen, H., Zhang, D., & Ye, W. (2017). Pericyte-targeting prodrug overcomes tumor resistance to vascular disrupting agents. J Clin Invest, 127, 3689–3701. https://doi.org/10.1172/JCI94258.CrossRefPubMedPubMedCentral

148.

Loeffler, M., Krüger, J. A., Niethammer, A. G., & Reisfeld, R. A. (2006). Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake. J Clin Invest, 116, 1955–1962. https://doi.org/10.1172/JCI26532.CrossRefPubMedPubMedCentral

149.

Wen, Y., Wang, C.-T., Ma, T.-T., Li, Z. Y., Zhou, L. N., Mu, B., Leng, F., Shi, H. S., Li, Y. O., & Wei, Y. Q. (2010). Immunotherapy targeting fibroblast activation protein inhibits tumor growth and increases survival in a murine colon cancer model. Cancer Sci, 101, 2325–2332. https://doi.org/10.1111/j.1349-7006.2010.01695.x.CrossRefPubMed

150.

Chen, M., Xiang, R., Wen, Y., et al. (2015). A whole-cell tumor vaccine modified to express fibroblast activation protein induces antitumor immunity against both tumor cells and cancer-associated fibroblasts. Sci Rep, 5, 14421. https://doi.org/10.1038/srep14421.CrossRefPubMedPubMedCentral

151.

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

152.

Ghobadi, A. (2018). Chimeric antigen receptor T cell therapy for non-Hodgkin lymphoma. Curr Res Transl Med, 66, 43–49. https://doi.org/10.1016/j.retram.2018.03.005.CrossRefPubMedPubMedCentral

153.

Schuberth, P. C., Hagedorn, C., Jensen, S. M., et al. (2013). Treatment of malignant pleural mesothelioma by fibroblast activation protein-specific re-directed T cells. J Transl Med, 11, 1–11. https://doi.org/10.1186/1479-5876-11-187.CrossRef

154.

Kakarla, S., Chow, K. K. H., Mata, M., et al. (2013). Antitumor effects of chimeric receptor engineered human T cells directed to tumor stroma. Mol Ther, 21, 1611–1620. https://doi.org/10.1038/mt.2013.110.CrossRefPubMedPubMedCentral

155.

Wang, L.-C. S., Lo, A., Scholler, J., et al. (2014). Targeting fibroblast activation protein in tumor stroma with chimeric antigen receptor T cells can inhibit tumor growth and augment host immunity without severe toxicity. Cancer Immunol Res, 2, 154–166. https://doi.org/10.1158/2326-6066.CIR-13-0027.CrossRefPubMed

156.

Tran, E., Chinnasamy, D., Yu, Z., et al. (2013). Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia. J Exp Med, 210, 1125–1135. https://doi.org/10.1084/jem.20130110.CrossRefPubMedPubMedCentral

157.

Gulati, P., Ruhl, J., Kannan, A., et al. (2018). Aberrant Lck signal via CD28 Costimulation augments antigen-specific functionality and tumor control by redirected T cells with PD-1 blockade in humanized mice. Clin Cancer Res, 24, 3981–3993. https://doi.org/10.1158/1078-0432.CCR-17-1788.CrossRefPubMed

158.

Aghajanian, H., Kimura, T., Rurik, J. G., et al. (2019). Targeting cardiac fibrosis with engineered T cells. Nature, 573, 430–433. https://doi.org/10.1038/s41586-019-1546-z.CrossRefPubMedPubMedCentral

Springer Medizin

The role of fibroblast activation protein in health and malignancy

Abstract

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2020

Epigenetic dynamics in cancer stem cell dormancy

Preface

Unraveling mucin domains in cancer and metastasis: when protectors become predators

Collagen biology making inroads into prognosis and treatment of cancer progression and metastasis