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 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 as coherent cell sheets when stimulated with 12-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 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 tyrosine 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 in 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 lines 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.
Nabeshima
K
K
Department of Pathology, Miyazaki Medical College, Kiyotake, Japan.
Shimao
Y
Y
Inoue
T
T
Itoh
H
H
Kataoka
H
H
Koono
M
M
D000230:Adenocarcinoma / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D051178:alpha Catenin
C495273:CTNNA1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D011994:Recombinant Proteins; D051178:alpha Catenin; D017228:Hepatocyte Growth Factor