A Novel Mechanism of Crosstalk between Fibroblast Growth Factor Receptor and Integrin alphav beta3

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590446
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Osaka University
• Principal Investigator: MORI Seiji 大阪大学, 医学(系)研究科(研究院), 助教 (90467506)
• Co-Investigator(Kenkyū-buntansha): MATSUURA Nariaki 大阪大学, 大学院医学系研究科, 教授 (70190402) ; KAWAGUCHI Naomasa 大阪大学, 大学院医学系研究科, 準教授 (70224748) ; HAMADA Yoshinosuke 大阪大学, 大学院医学系研究科, 特任助教 (10362683)
• Research Collaborator: TAKADA Yoshikazu University of Carifornia Davis, 教授
• Project Period (FY): 2011 – 2013
• Keywords: インテグリン / FGF / FGF受容体 / 血管新生

Research Abstract

We previously reported that Fibroblast growth factor 1 (FGF1) binds both FGF receptor and integrin avb3, and also reported that integrin binding defective FGF1 mutant (Arg 50 to Glu, R50E) is defective in a fibroblast cell proliferation and migration. In this study, we tested if the interaction between FGF1 and integrin avb3 is required for angiogenesis and tumor growth. Here we demonstrated that FGF1-R50E is defective in inducing endothelial cell migration and tube formation, and suppressed wild-type FGF1-induced signaling (dominant-negative effect) in vitro. FGF1-R50E suppressed growth of colon cancer cells which subcutaneously transplanted in nude mice. These findings suggest that FGFR and integrin avb3 crosstalk through direct integrin binding to FGF, and that R50E acts as an antagonist to FGFR. We proposed that FGF1-R50E has potential as an anti-angiogenesis and anti-cancer therapeutic.

Research Products

• [Journal Article] FGF1 (fibroblast growth factor 1 (acidic)) (2014)
  • Author(s): Mori S. and Takada Y.
  • Journal Title: Atlas Genet Cytogenet Oncol Haematol Volume: 18(3) Pages: 164-168
  • DOI: 10.4267/2042/53482
• [Journal Article] Crosstalk between Fibroblast Growth Factor (FGF) Receptor and Integrin through Direct Integrin Binding to FGF and Resulting Integrin-FGF-FGFR Ternary Complex Formation (2013)
  • Author(s): Mori S. and Takada Y.
  • Journal Title: Med. Sci. Volume: 1 Pages: 20-36
  • DOI: 10.1371/journal.pone.0057927
  • Peer Reviewed
• [Journal Article] A dominant-negative FGF1 mutant (the R50E mutant) suppresses tumorigenesis and angiogenesis (2013)
  • Author(s): Mori S, Tran V, Nishikawa K, Kaneda T, Hamada Y, Kawaguchi N, Fujita M, Takada YK, Matsuura N, Zhao M, Takada Y.
  • Journal Title: PLoS One Volume: 8 Pages: e57927
  • DOI: 10.1371/journal.pone.0057927
  • Peer Reviewed
• [Journal Article] Platelet-Derived Growth Factor Regulates Breast Cancer Progression viaβ-Catenin Expression (2011)
  • Author(s): Yokoyama Y, Mori S, Hamada Y, Kawaguchi N, Matsuura N.
  • Journal Title: Pathobiology Volume: 78 Pages: 253-260
  • DOI: 10.1159/000328061
  • Peer Reviewed
• [Presentation] The Direct Binding of Fibroblast Growth Factor-1 (FGF1) to Integrins is Rquired for Agiogenesis (2013)
  • Author(s): Mori S, Nishikawa K, Kodaira M, Ito A, Takada Y, Matsuura N
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸市神戸国際会議場
  • Year and Date: 20131203-06
• [Presentation] Bidirectional effect of Fibroblast growth factor 1 (FGF1) on epithelial-mesenchymal transition (EMT) depends on interaction of integrinαv ß3 and FGF1 in mammary epithelial cells (2013)
  • Author(s): Kodaira M, Mori S, Ito A, Okazaki M, Takada Y, Matsuura N
  • Organizer: 第36回日本分生物学会年会
  • Place of Presentation: 神戸市神戸国際会議場
  • Year and Date: 20131203-06
• [Presentation] 線維芽細胞増殖因子(FGF1)とインテグリンαvβ3の結合は血管新生に必要である (2013)
  • Author(s): 森誠司、河口直正、高田義一、松浦成昭
  • Organizer: 第17回日本適応医学会学術集会
  • Place of Presentation: さいたま市ソニックシティ
  • Year and Date: 20130628-29
• [Presentation] FGF1 mutant, integrin binding defective, suppresses angiogenesis (2012)
  • Author(s): Mori S, Nishikawa K, Kaneda T, Kamei A, Kodaira M, Kodaira M, Ito A, Takada Y, Matsuura N
  • Organizer: The 7th International Symposium on Cancer Research and Therapy
  • Place of Presentation: 東京都東京会館
  • Year and Date: 20121109-10