The HGF/SF-induced phosphorylation of paxillin, matrix adhesion, and invasion of prostate cancer cells were suppressed by NK4, an HGF/SF variant

Hepatocyte growth factor/scatter factor (HGF/SF) plays a crucial role in ca ncer cell migration, matrix adhesion, invasion, and angiogenesis, via the p hosphorylation of the c-met tyrosine kinase. This study examined the abilit y of NK4, a recently discovered HGF/SF variant, to inhibit the influence of HGF/SF on cell-matrix interaction, paxillin phosphorylation, and invasion of prostate cancer cells. HGF/SF was shown to dramatically enhance tumour c ell motility, invasion, cell-matrix adhesion, together with an increase in the degree of paxillin phosphorylation and formation of focal adhesion comp lexes. However, these HGF/SF-induced effects were suppressed by the presenc e of NK4. NK4 effectively inhibited the degree of HGF/SF-induced paxillin p hosphorylation and matrix adhesion. As a consequence, the matrix invasion o f these prostate cancer cells was also suppressed by NK4. In conclusion, th is study shows that these HGF/SF-enhanced events, which are critical steps in metastasis, can be inhibited through the addition of NK4, thus warrantin g further in vivo studies on the implication of NK4 as a potential antimeta stasis agent in prostate cancer. (C) 2001 Academic Press.