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Nk4, a new HGF/SF variant, is an antagonist to the influence of HGF/SF on the motility and invasion of colon cancer cells
Author(s) -
Parr Christian,
Hiscox Steven,
Nakamura Toshikazu,
Matsumoto Kunio,
Jiang Wen G.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000215)85:4<563::aid-ijc19>3.0.co;2-d
Subject(s) - hepatocyte growth factor , motility , cancer research , angiogenesis , kringle domain , matrigel , cell migration , urokinase receptor , metastasis , biology , chemistry , receptor , cancer , medicine , cell , plasmin , microbiology and biotechnology , biochemistry , enzyme
Hepatocyte Growth Factor/Scatter Factor (HGF/SF) is a heterodimeric molecule that plays a key role in the regulation of migration, invasion and angiogenesis in cancer, via activation of its receptor, c‐met. HGF/SF is composed of an α‐chain, containing the N‐terminal hairpin domain and 4 kringle domains, plus the serine protease‐like β‐chain. We have examined here the properties of NK4, an HGF variant containing the N‐terminal hairpin plus the 4 kringle domains, on tumour cell proliferation, dissociation and invasion using human colorectal cancer cells (HT115). The expression of HGF/SF and its receptor was also examined by RT‐PCR and Western blotting. Analysis revealed NK4 to be an HGF/SF antagonist that, at a wide range of concentrations, did not exert any biological effects of its own. HT115 cells were shown to express the HGF/SF receptor mRNA and protein. HGF/SF‐induced receptor tyrosine phosphorylation was suppressed, in a dose‐dependent manner, upon addition of NK4, whereas the addition of NK4 alone caused no phosphorylation. Tumour cell motility was induced by HGF and inhibited by NK4. Furthermore, HGF/SF induced the invasion of cells through Matrigel basement membrane components, and again this induced invasion was suppressed by NK4. Our results show that the ability of HGF/SF to stimulate tumour cell motility and invasion, properties required for metastatic spread, can be inhibited by NK4. Thus, NK4 may have an important role in the control of cancer metastasis. Int. J. Cancer 85:563–570, 2000. © 2000 Wiley‐Liss, Inc.