title: Fibroblast activation protein regulates tumor-associated fibroblasts             and epithelial ovarian cancer cells.
abstract: The fibroblast activation protein (FAP) is a cell surface serine protease             which has emerged as a specific marker of tumor-associated fibroblasts (TAFs).             FAP has been shown to have both in vitro dipeptidyl peptidase and collagenase             activity. However, the biological function of FAP in the tumor microenvironment             is largely unknown. In this study, we first show that TAFs isolated from ovarian             cancer samples have the characteristics of stem cells. To explore the functional             role of FAP, the protein was silenced by siRNA lentiviral vector transfection.             FAP silencing inhibited the growth of TAFs in vitro, accompanied with cell cycle             arrest at the G2 and S phase in TAFs. FAP silencing also reduced the stem cell             marker gene expression in TAFs. SKOV3 cells do not express FAP. Although FAP-silenced             SKOV3 cells induced ovarian tumors, the rate of tumor growth was significantly             decreased, as shown in the xenograft mouse model. TAF phenotypes in the xenograft             tumor tissues were further assayed by immunohistochemistry. The expression of             TAF markers, including fibroblast-specific protein, FAP, smooth muscle actin,             desmin, vascular endothelial growth factor and fibroblast growth factor was decreased             in the tumor stroma induced by FAP-silenced SKOV3 cells. In conclusion, FAP is             an important regulator of the microenvironment in tumor formation and targeting             FAP is a potential therapeutic strategy to combat ovarian cancer.
authors.affiliation: Shanghai Jiaotong University, Shanghai, People's Republic of China. laidongmei@hotmail.com
authors.forename: Dongmei
authors.initials: D
authors.lastname: Lai
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Wang
mesh_terms: D059786:Abnormal Karyotype; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D048430:Cell Shape; D002869:Chromosome Aberrations; D010450:Endopeptidases; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000502:physiology; D059565:G2 Phase Cell Cycle Checkpoints; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009375:Neoplasms, Glandular and Epithelial / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000502:physiology; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D000943:Antigens, Differentiation; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha