An FGFR inhibitor converts the tumor promoting effect of TGF-beta by the induction of fibroblast-associated genes of hepatoma cells

作者：Zhang, H-R; Wang, X-D; Yang, X.; Chen, D.; Hao, J.; Cao, R.; Wu, X-Z^*

来源：Oncogene, 2017, 36(27): 3831-3841.

DOI：10.1038/onc.2016.512

• EPITHELIAL-MESENCHYMAL TRANSITION
• GROWTH-FACTOR-BETA
• HEPATOCELLULAR-CARCINOMA
• CANCER
• PROGRESSION
• EXPRESSION
• ACTIVATION
• AZD4547

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 beta (TGF-beta) 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-beta increases the secretion of FGFs, further promoting the malignant biological properties of tumors. However, during wound healing, sufficient TGF-beta together with moderate FGFs lead to matrix deposition and the formation of fibrotic scars. In the present study, TGF-beta 1 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-beta 1 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-beta on the hepatocellular carcinoma cells from tumor promotion into tumor inhibition by enhancing the induction effect of TGF-beta 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.

• 出版日期2017-7-6
• 单位天津医科大学