@article{oai:repo.qst.go.jp:00048799, author = {Miura, Taichi and Fujita, Mayumi and Kawano, Mitsuko and Imadome, Kaori and Yasuda, Takeshi and Shoko, Nishihara and Imamura, Toru and Masuzawa, Mikio and Imai, Takashi and Nakayama, Fumiaki and 三浦 太一 and 藤田 真由美 and 川野 光子 and 今留 香織 and 安田 武嗣 and 西原 祥子 and 今村 亨 and 増澤 幹男 and 今井 高志 and 中山 文明}, journal = {Clinical and Translational Radiation Oncology}, month = {Nov}, note = {Background and purpose: Angiosarcoma is associated with a poor prognosis and is treated with radiotherapy. Although FGF1 is a potential radioprotector, the influence of FGF1 on the malignancy of angiosarcoma remains unknown. Materials and methods: Highly stable FGF1 mutants, which exhibit stronger mitogenic activity than wild-type FGF1, were examined as strong radioprotectors and signaling agonists to clarify the effects of FGF1 on the murine angiosarcoma cell line ISOS-1. Results: FGF1 mutants reduced colony formation by and the in vitro invasion and migration of ISOS-1 cells, in addition to an increase in radiosensitivity to X-rays. In contrast, an FGFR inhibitor blocked the inhibitory effects of FGF1 mutants on colony formation, invasion, and migration. siRNA targeting the Fgfr1 gene showed that strong FGFR1 signaling reduced colony formation by ISOS-1 cells. However, the FGF1 mutant reduced the activation of VEGFRs and EGFRs in ISOS-1 cells more strongly than wild-type FGF1. Moreover, the inhibition of VEGFRs and EGFRs synergistically reduced colony formation by and invasion and migration of ISOS-1 cells. Conclusion: These results suggest that strong FGF1 signaling exerts not only radioprotective effects, but also inhibitory effects on proliferative and metastatic capacities of angiosarcoma through the dual inhibition of EGFR and VEGFR pathways.}, pages = {83--90}, title = {Strong radioprotective FGF1 signaling down-regulates proliferative and metastatic capabilities of the angiosarcoma cell line, ISOS-1, through the dual inhibition of EGFR and VEGFR pathways}, volume = {7}, year = {2017} }