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

• 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
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• 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)). (2013)
  • Author(s): Mori S, and Takada Y.
  • Journal Title: Atlas Genet Cytogenet Oncol Haematol. Volume: Published in Atlas Database Issue: 3 Pages: 164-168
  • DOI: 10.4267/2042/53482
  • Open Access
• [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: Medical Sciences Volume: 1 Issue: 1 Pages: 20-36
  • DOI: 10.3390/medsci1010020
  • Peer Reviewed
• [Journal Article] Transplantation of myoblast sheets that secrete the novel peptide SVVYGLR improves cardiac function in failing hearts. (2013)
  • Author(s): Uchinaka A, Kawaguchi N, Hamada Y, Mori S, Miyagawa S, Saito A, Sawa Y, Matsuura N.
  • Journal Title: Cardiovascular Research Volume: 99 Issue: 1 Pages: 102-110
  • DOI: 10.1093/cvr/cvt088
  • Peer Reviewed
• [Journal Article] A novel diagnostic method for detection of lymph node metastases (2013)
  • Author(s): Matsuura N, Uchinaka A, Mori S.
  • Journal Title: Nihon Geka Gakkai Zasshi. Volume: 114 Pages: 4-8
  • NAID: 110009578665
• [Journal Article] A Dominant-Negative FGF1 Mutant (the R50E Mutant) Suppresses Tumorigenesis and Angiogenesis. (2012)
  • Author(s): Mori S.
  • Journal Title: PLoS One. Volume: 8(2) Issue: 2 Pages: 20-36
  • DOI: 10.1371/journal.pone.0057927
  • Peer Reviewed
• [Journal Article] The preparation of PLLA/calcium phosphate hybrid composite and its evaluation of biocompatibility. (2012)
  • Author(s): Hamada Y, Fujitani W, Kawaguchi N, Daito K, Niido T, Uchinaka A, Mori S, Kojima Y, Manabe M, Nishida K, Arita K, Nakano T, Matsuura N.
  • Journal Title: Dent Mater J. Volume: 31 Pages: 1087-1096
  • NAID: 10031126094
  • Peer Reviewed
• [Journal Article] Transplantation of elastin-secreting myoblast sheets improves cardiac function in infarcted rat heart. (2012)
  • Author(s): Uchinaka A.
  • Journal Title: Mol Cell Biochem. Volume: 368(1-2) Issue: 1-2 Pages: 203-14
  • DOI: 10.1007/s11010-012-1361-4
  • Peer Reviewed
• [Journal Article] Platelet-Derived Growth Factor Regulates Breast Cancer Progression via・-Catenin Expression (2011)
  • Author(s): Yokoyama, Y., Mori, S., Hamada, Y., Hieda, M., Kawaguchi, N., Shaker, M., Tao, Y., Yoshidome, K., Tsujimoto, M., Matsuura, N.
  • Journal Title: Pathobiology Volume: 78 Issue: 5 Pages: 253-260
  • DOI: 10.1159/000328061
  • Peer Reviewed
• [Journal Article] Aberrant expression of disintegrin-metalloprotease proteins in the formation and progression of uterine cervical cancer (2011)
  • Author(s): Shaker M, Matsuura N., et al
  • Journal Title: Pathobiology Volume: 78(3) Issue: 3 Pages: 149-61
  • DOI: 10.1159/000324314
  • 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
• [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
• [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
• [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: 埼玉県さいたま市ソニックシティ
• [Presentation] The Direct Binding of Fibroblast Growth Factor-1 (FGF1) to Integrins is Rquired for Agiogenesis. (2013)
  • Author(s): Seiji Mori, kyoko Nishikawa, Moe Kodaira, Ayano Ito, Yoshikazu Takada, Nariaki Matsuura
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 兵庫県神戸市 神戸国際会議場
• [Presentation] Bidirectional effect of Fibroblast growth factor 1 (FGF1) on epithelial-mesenchymal transition (EMT) (2013)
  • Author(s): Moe Kodaira, Seiji Mori, Ayano Ito, Mika Okazaki, Yoshikazu Takada, Nariaki Matsuura
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 兵庫県神戸市 神戸国際会議場
• [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
• [Presentation] FGF1 MUTANT, INTEGRIN BINDING-DEFECTIVE, SUPRESSES ANGIOGENESIS. (2012)
  • Author(s): Seiji Mori, Kyoko Nishikawa, Teruya Kaneda, Ayako Kamei, Moe Kodaira, Yoshikazu Takada, Nariaki Matsuura.
  • Organizer: International Symposium on Cancer Research and Therapy
  • Place of Presentation: Tokyo, Marunouchi, Tokyo-Kaikan