NK4 gene therapy targeting HGF-MET and angiogenesis
NK4 gene therapy targeting HGF-MET and angiogenesis
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DOI：
10.2741/2813
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发表时间：
2008-01-01
影响因子：
3.1
通讯作者：
Nakamura, Toshikazu
中科院分区：
文献类型：
--
作者：
Matsumoto, Kunio;Nakamura, Toshikazu
基于肝细胞生长因子（HGF）和Met/HGF受体酪氨酸激酶在肿瘤侵袭和转移中发挥一定作用的背景，NK 4被分离出来作为针对HGF和Met之间功能关联的竞争性拮抗剂。NK 4是HGF的内部片段，由N-末端和四个kringle结构域组成。独立于其HGF拮抗剂作用，NK 4抑制血管内皮细胞生长因子和碱性成纤维细胞生长因子以及HGF诱导的血管生成，表明NK 4是一种双功能分子，作为HGF拮抗剂和血管生成抑制剂。在不同类型癌症的实验模型中，NK 4基因治疗抑制Met受体活化，这与抑制肿瘤侵袭和转移有关。同样，NK 4基因治疗抑制肿瘤血管生成，从而抑制血管生成依赖性肿瘤生长。用NK 4进行的癌症治疗抑制恶性肿瘤在肿瘤生长和扩散方面都是“静止的”。NK 4作为人类潜在的癌症治疗方法值得进一步研究和关注。
Based on the background that hepatocyte growth factor (HGF) and Met/HGF receptor tyrosine kinase play a definite role in tumor invasion and metastasis, NK4 was isolated as a competitive antagonist against functional association between HGF and Met. NK4 is an internal fragment of HGF and composed of the N-terminal and four kringle domains. Independently on its HGF-antagonist action, NK4 inhibited angiogenesis induced by vascular endothelial cell growth factor and basic fibroblast growth factor, as well as HGF, indicating that NK4 is a bifunctional molecule that acts as an HGF-antagonist and angiogenesis inhibitor. In experimental models of distinct types of cancers, NK4 gene therapy inhibited Met receptor activation and this was associated with inhibition of tumor invasion and metastasis. Likewise, NK4 gene therapy inhibited tumor angiogenesis, thereby suppressing angiogenesis-dependent tumor growth. Cancer treatment with NK4 suppresses malignant tumors to be 'static' in both tumor growth and spreading. NK4 warrants further investigation and attention as potential cancer therapy for humans.