NK4 gene therapy targeting HGF-Met and angiogenesis (original) (raw)

IMR Press / FBL / Volume 13 / Issue 5 / DOI: 10.2741/2813

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article

NK4 gene therapy targeting HGF-Met and angiogenesis

Affiliation

1 Division of Tumor Dynamics and Regulation, Kanazawa University Cancer Research Institute, 13-1 Takaramachi, Kanazawa

2 Division of Molecular Regenerative Medicine, Osaka University Graduate School of Medicine, 2-2-B7, Yamadaoka, Suita, Osaka 565-0871, Japan

*Author to whom correspondence should be addressed.

Published: 1 January 2008

Abstract

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.

Front. Biosci. (Landmark Ed) Print ISSN 2768-6701 Electronic ISSN 2768-6698

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