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

成纤维细胞生长因子受体与整合素αvβ3串扰的新机制

• 批准号: 23590446
• 负责人: MORI Seiji
• 金额: $ 3.08万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590446/
• 关键词: インテグリン; FGF; FGF受容体; 血管新生

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.

我们以前报道了成纤维细胞生长因子1（FGF 1）结合FGF受体和整合素avb 3，并且还报道了整合素结合缺陷型FGF 1突变体（Arg 50 to Glu，R50 E）在成纤维细胞增殖和迁移中有缺陷。在这项研究中，我们测试了FGF 1和整合素avb 3之间的相互作用是否是血管生成和肿瘤生长所必需的。在这里，我们证明了FGF 1-R50 E在体外诱导内皮细胞迁移和管形成方面存在缺陷，并抑制野生型FGF 1诱导的信号传导（显性负效应）。FGF 1-R50 E抑制结肠癌细胞裸鼠皮下移植瘤的生长。这些发现表明，FGFR和整联蛋白avb 3通过直接整联蛋白结合FGF而相互干扰，并且R50 E充当FGFR的拮抗剂。我们提出FGF 1-R50 E具有作为抗血管生成和抗癌治疗剂的潜力。

项目成果

A dominant-negative FGF1 mutant (the R50E mutant) suppresses tumorigenesis and angiogenesis.

• DOI: 10.1371/journal.pone.0057927
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Mori S;Tran V;Nishikawa K;Kaneda T;Hamada Y;Kawaguchi N;Fujita M;Saegusa J;Takada YK;Matsuura N;Zhao M;Takada Y
• 通讯作者: Takada Y

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

血管生成需要成纤维细胞生长因子 (FGF1) 和整合素 αvβ3 的结合

• 发表时间: 2013
• 作者: 森誠司;河口直正;高田義一;松浦成昭
• 通讯作者: 松浦成昭

Aberrant expression of disintegrin-metalloprotease proteins in the formation and progression of uterine cervical cancer

解整合素金属蛋白酶蛋白的异常表达在宫颈癌的形成和进展中

• 发表时间: 2011
• 期刊: Pathobiol
• 作者: M. Shaker;Y. Yokoyama;S. Mori;M. Tsujimoto;N. Kawaguchi;T. Kiyono;T. Nakano;N. Matsuura
• 通讯作者: N. Matsuura

FGF1 mutant, integrin binding defective, suppresses angiogenesis

FGF1 突变体，整合素结合缺陷，抑制血管生成

• 发表时间: 2012
• 作者: Mori S;Nishikawa K;Kaneda T;Kamei A;Kodaira M;Kodaira M;Ito A;Takada Y;Matsuura N
• 通讯作者: Matsuura N

The preparation of PLLA/calcium phosphate hybrid composite and its evaluation of biocompatibility

• DOI: 10.4012/dmj.2012-117
• 发表时间: 2012-11-01
• 期刊: DENTAL MATERIALS JOURNAL
• 影响因子: 2.5
• 作者: Hamada, Yoshinosuke;Fujitani, Wataru;Matsuura, Nariaki
• 通讯作者: Matsuura, Nariaki