title: An FGFR inhibitor converts the tumor promoting effect of TGF-β by the induction of fibroblast-associated genes of hepatoma cells.
abstract: Tumors consistently mimic wound-generating chronic inflammation; however, why they do not heal like wounds with fibrotic scars remains unknown. The components of the tumor microenvironment, such as transforming growth factor β (TGF-β) and fibroblast growth factors (FGFs), may account for this phenomenon. Tumor formation involves continuous activation of the FGF pathway, whereas the repair of tissue injury is a self-limiting process accompanied with controlled activation of the FGF pathway. In the tumor microenvironment TGF-β increases the secretion of FGFs, further promoting the malignant biological properties of tumors. However, during wound healing, sufficient TGF-β together with moderate FGFs lead to matrix deposition and the formation of fibrotic scars. In the present study, TGF-β1 combined with AZD4547, an FGF receptor (FGFR) inhibitor, transformed hepatoma cells into less malignant fibroblast-like cells with respect to morphology, physiological properties, and gene expression profiles. In vivo experiments showed that TGF-β1 combined with AZD4547 not only inhibited tumor growth but also promoted tumor parenchyma fibrosis. Our results indicate that FGFR inhibitor treatment converts the effect of TGF-β on the hepatocellular carcinoma cells from tumor promotion into tumor inhibition by enhancing the induction effect of TGF-β on some fibroblast-associated genes. Converting human liver cancer cells into less malignant fibroblast-like cells and inducing tumor parenchyma cell fibrosis provides an alternative strategy for limiting tumor progression.
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.|Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin's Clinical Research Center for Cancer, Tianjin, China.
authors.forename: H-R
authors.initials: HR
authors.lastname: Zhang
authors.affiliation: Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: X-D
authors.initials: XD
authors.lastname: Wang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.|Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin's Clinical Research Center for Cancer, Tianjin, China.
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.|Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin's Clinical Research Center for Cancer, Tianjin, China.
authors.forename: J
authors.initials: J
authors.lastname: Hao
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.|Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin's Clinical Research Center for Cancer, Tianjin, China.
authors.forename: R
authors.initials: R
authors.lastname: Cao
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.|Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin's Clinical Research Center for Cancer, Tianjin, China.
authors.forename: X-Z
authors.initials: XZ
authors.lastname: Wu
mesh_terms: D000818:Animals; D001549:Benzamides; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010879:Piperazines; D011720:Pyrazoles; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D059016:Tumor Microenvironment
chemical_list: C572463:AZD4547; D001549:Benzamides; D010879:Piperazines; D011720:Pyrazoles; D017468:Receptors, Fibroblast Growth Factor; D053773:Transforming Growth Factor beta1