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Hepatocyte growth factor/scatter factor induces not only scattering but also cohort migration of human colorectal-adenocarcinoma cells

, : Hepatocyte growth factor/scatter factor induces not only scattering but also cohort migration of human colorectal-adenocarcinoma cells. International Journal of Cancer 78(6): 750-759, Dec 9

We presented earlier a 2-dimensional cell-motility ass using a highly metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1 as a motility model of tumor cells of epithelial origin. In this model, L-10 cells moved coherent cell sheets when stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA), and we called this type of movement "cohort migration". Electron- and immuno electron-microscope study of the migrating cell sheets demonstrated localized release from cell-cell adhesion only at the lower portion of the cells with loss of E-cadherin immunoreactivity, and this change was associated with increased tyrosin phosphorylation of the E-cadherin-catenin complex, including beta-catenin. In the present study, to obtain evidence to support the relevance of our model to carcinoma-cell movement vivo, we sought a naturally occurring motogenic factor(s) able to induce this cohort migration. Among the factors examined, hepatocyte growth factor/scatter factor (HGF/SF) clearly induced cohort migration of L-10 cells. Additionally, not only L-10 but several other human colorectal-carcinoma cell line showed this type of migration in response to HGF/SF, while yet others showed scattering-type motility. In this HGF/SF induced migration, localized release from cell-cell adhesion was induced only at the lower portion of the cells, allowing them to extend leading lamellae, whereas close cell-cell contacts remained at the upper portion of the cells, as seen in TPA-induced cohort migration. Scattering-type 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 the scattering-type cell lines, expressed more c-Met protein and less E-cadherin than L-10, which showed cohort-type migration. HGF/SF treatment of LoVo reduced the amount of alpha-catenin complexed with E-cadherin more markedly than in L-10, but in both cell lines this reduction was not accompanied by increased tyrosine phosphorylation of beta-catenin, suggesting the presence of a mechanism other than phosphorylation for release from cell-cell adhesion during cell motility.


PMID: 9833769

DOI: 10.1002/(sici)1097-0215(19981209)78:6<750::aid-ijc13>;2-#

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