HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR INDUCES NOT ONLY SCATTERING BUT ALSO COHORT MIGRATION OF HUMAN COLORECTAL-ADENOCARCINOMA CELLS

We presented earlier a 2-dimensional cell-motility assay using a highl y metastatic variant (L-10) of human rectal-adenocarcinoma cell line R CM-1 as a motility model of tumor cells of epithelial origin, In this model, L-IO cells moved as coherent cell sheets when stimulated with 1 2-O-tetradecanoylphorbol-13-acetate (TPA), and we called this type of movement ''cohort migration'', Electron- and immunoelectron-microscope study of the migrating cell sheets demonstrated localized release fro m cell-cell adhesion only at the lower portion of the cells with loss of E-cadherin immunoreactivity, and this change was associated with in creased tyrosine phosphorylation of the E-cadherin-catenin complex, in cluding beta-catenin, In the present study, to obtain evidence to supp ort the relevance of our model to carcinoma-cell movement In vivo, we sought a naturally occurring motogenic factor(s) able to induce this c ohort migration. Among the factors examined, hepatocyte growth factor/ scatter factor (HGF/SF) clearly induced cohort migration of L-IO cells . Additionally, not only L-10 but several other human colorectal-carci noma cell lines showed this type of migration in response to HGF/SF, w hile yet others showed scattering-type motility, In this HGF/SF-induce d migration, localized release from cell-cell adhesion was induced onl y at the lower portion of the cells, allowing them to extend leading l amellae, whereas close cell-cell contacts remained at the upper portio n of the cells, as seen in TPA-induced cohort migration, Scattering-ty pe cell lines tended to express more c-Met (receptor for HGF/SF) mRNA than the cell lines that showed cohort-type migration. LoVo, one of th e scattering-type cell lines, expressed more c-Met protein and less E- cadherin than L-10, which showed cohort-type migration, HGF/SF treatme nt of LoVo reduced the amount of alpha-catenin complexed with E-cadher in more markedly than in L-10, but in both cell lines this reduction w as not accompanied by increased tyrosine phosphorylation of beta-caten in, suggesting the presence of a mechanism other than phosphorylation for release from cell-cell adhesion during cell motility, (C) 1998 Wil ey-Liss, Inc.