Inhibitory effects of HGF antagonist on invasion/metastasis of tumor cells.

HGF拮抗剂对肿瘤细胞侵袭/转移的抑制作用。

• 批准号: 07557199
• 负责人: NAKAMURA Toshikazu
• 金额: $ 4.16万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557199/
• 关键词: HGF; HGF antagonist; NK4; c-Met; tumor; tumor-stromal interaction; invasion; metastasis; NK4; 浸潤・転移; 血管新生; 浸潤・転移抑制剤; 基底膜浸潤; コラーゲンゲル内浸潤; c-met; 癌細胞; 腫瘍; 癌浸潤・転移; 増殖因子; サイトカイン; レセプター

Invasion and metastasis of tumor cells follows their interaction with stromal cells. Hepatocyte growth factor (HGF) is a mesenchymal- or stromal-derived mediator that affects the growth and the invasiveness of tumor cells. We prepared an antagonistic molecule, designated as HGF/NK4, from partially digested recombinant HGF.HGF/NK4 competitively inhibited the HGF binding to its receptor c-Met, and abrogated the mitogenic, motpgenic, and morphogenic actions of HGF.In addition, HGF/NK4 almost completely suppressed HGF-induced scattering and invasion of tumor cells in vitro. Furthermore, HGF/NK4 drastically inihibited growth, invasion, and metastasis of tumor cells subcutaneously implanted into nude mouse. These results suggest that there is a unique therapeutic potential for HGF/NK4 to prevent tumor invasion and metastasis.

肿瘤细胞的侵袭和转移遵循它们与基质细胞的相互作用。肝细胞生长因子（HGF）是一种间质或基质衍生的介质，影响肿瘤细胞的生长和侵袭。我们从部分消化的重组人肝细胞生长因子（HGF）中制备了一种拮抗分子HGF/NK_4，HGF/NK_4能竞争性抑制HGF与受体c-Met的结合，阻断HGF的促有丝分裂、促运动和促形态发生作用，并在体外几乎完全抑制HGF诱导的肿瘤细胞的扩散和侵袭。HGF/NK 4对裸鼠皮下移植瘤的生长、侵袭和转移有明显的抑制作用。这些结果表明，HGF/NK 4在预防肿瘤侵袭和转移方面具有独特的治疗潜力。

项目成果

Y.Matsuda: "Prevential and therapeutic effects in rats of hepatocyte growth factor on liver fibrosis/cirrhosis." Hepatology. (in press). (1997)

Y.Matsuda：“肝细胞生长因子对大鼠肝纤维化/肝硬化的预防和治疗作用。”

G.Shiota: "Serum hepatocyte growth factor level : its clinical implication." Hepatology. 21. 106-112 (1995)

G.Shiota：“血清肝细胞生长因子水平：其临床意义。”

W.G.Jiang: "Inhibition of HGF/SF-induced membrane ruffling and cell motility by transient elevation of cytosolic free Ca^<2+>." Exp.Cell Res.220. 424-433 (1995)

W.G.Jiang：“通过胞质游离 Ca^2 的瞬时升高抑制 HGF/SF 诱导的膜波纹和细胞运动。”

S.Mizuno et al.: "Hepatocyte growth factor prevents renal fibrosis and dysfunction in mouse model of chronio renal disease." J.Clin.Invest.(in press.). (1998)

S.Mizuno 等人：“肝细胞生长因子可预防慢性肾病小鼠模型中的肾纤维化和功能障碍。”

中村 敏一: "分子生物学プロトコール改訂版 タンパク質の生化学的分析" 南江堂(印刷中), (1997)

Toshikazu Nakamura：“修订的分子生物学实验方案：蛋白质的生化分析”Nankodo（印刷中），（1997 年）