Role of FGF10 on tumorigenesis by MS‐K

• Published in: Genes to cells : devoted to molecular & cellular mechanisms Vol. 19; no. 2; pp. 112 - 125
• Main Authors: Sugimoto, Kenkichi, Yoshida, Suzuka, Mashio, Yuka, Toyota, Naoka, Xing, Yanjiang, Xu, Henan, Fujita, Yuki, Huang, Zhijun, Touma, Maki, Wu, Qiong
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.02.2014
• Subjects: Animals; Autocrine signalling; Carcinogenesis - metabolism; Carcinogenesis - pathology; Cell Line, Tumor; Cell Proliferation; Fibroblast Growth Factor 10 - genetics; Fibroblast Growth Factor 10 - metabolism; Gene Knockdown Techniques; Human Umbilical Vein Endothelial Cells - metabolism; Human Umbilical Vein Endothelial Cells - pathology; Humans; Medical research; Mice; Molecular Sequence Data; Neoplasm Transplantation; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Rodents; Vascular endothelial growth factor
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/gtc.12118

Murine MS‐K and NFSA cell lines formed tumor after inoculation into mouse and both cell lines expressed high level of vascular endothelial growth factor‐A (vegf‐A) and produced same level of VEGF‐A. However, poor blood vessel formation, and necrosis was significantly observed in NFSA‐tumor, contrary to well‐developed blood vessel formation in MS‐K tumor. The microarray analysis showed high expression of fibroblast growth factor‐10 (fgf‐10) in MS‐K than NFSA. In this report, the role of fgf‐10 on tumor growth was studied. MS‐K enhanced more proliferation of endothelial cells by direct co‐culture than NFSA, and rFGF10 supported the proliferation of HUVEC in combination with VEGF‐A. fgf‐10‐knocked down MS‐K, MS‐K (fgf‐10‐KD), proliferated slower in vitro and the tumorigenicity of them was also slower than control. The blood vessel formation in these MS‐K (fgf‐10‐KD) clones was reduced compared with the MS‐K (normal). qPCR analysis showed the suppression of vegf‐A, vegf‐C and fgfr‐1‐expression in the MS‐K (fgf‐10‐KD) clones. Taken together, these results indicated that FGF10, which was produced from tumor cells, was essential for the proliferation of tumor cell itself and also supports proliferation of endothelial cells. Thus, FGF10 plays an important role for tumor growth by both paracrine and autocrine manner.