TY - JOUR
T1 - Role of α5β1 integrin in determining malignant properties of colon carcinoma cells
AU - Gong, Jiangen
AU - Wang, Dan Hui
AU - Sun, Lu Zhe
AU - Zborowska, Elizabeth
AU - Willson, James K.V.
AU - Brattain, Michael G.
PY - 1997
Y1 - 1997
N2 - We characterized the expression of α5β1 integrin in two distinct phenotypes of colon carcinoma cell lines. Highly invasive colon cell lines (designated Group I cell lines) expressed higher levels of integrin α5β1 mRNA and protein than did poorly invasive colon cell lines (designated Group III cell lines). The relatively high expression of integrin α5β1 in Group I cell lines resulted in strong enhancement of cell adhesion to fibronectin (FN) tissue culture plates, whereas Group III cell lines showed little or no enhancement of cell adhesion by coating. There was no significant difference between Group I and Group III cell lines with respect to cell adhesion to laminin and collagen IV. Cell adhesion to FN in Group I cells was mainly mediated by integrin α5β1 because a monoclonal antiα5 subunit antibody could block cell adhesion to FN, whereas anti-α2 and anti-α3 antibodies had no effect on cell adhesion to FN. The divergence of α5β1 expression in these two distinct colon carcinoma phenotypes suggested that high expression of α5β1 might contribute to malignant progression in this model system. To test this hypothesis, GEO cells, a Group III cell line that did not express α5 integrin, were transfected with the α5 subunit. Stable transfection of α5 sense cDNA into a typical GEO-limiting dilution clone led to the expression of α5 subunit mRNA and cell surface α5β1 protein. The α5 sense transfectants showed enhanced attachment to FN-coated plates and were more tumorigenic when the cells were injected into athymicnude mice. These results indicate that inappropriately high α5β1 integrin expression contributes to malignant progression in colon carcinoma.
AB - We characterized the expression of α5β1 integrin in two distinct phenotypes of colon carcinoma cell lines. Highly invasive colon cell lines (designated Group I cell lines) expressed higher levels of integrin α5β1 mRNA and protein than did poorly invasive colon cell lines (designated Group III cell lines). The relatively high expression of integrin α5β1 in Group I cell lines resulted in strong enhancement of cell adhesion to fibronectin (FN) tissue culture plates, whereas Group III cell lines showed little or no enhancement of cell adhesion by coating. There was no significant difference between Group I and Group III cell lines with respect to cell adhesion to laminin and collagen IV. Cell adhesion to FN in Group I cells was mainly mediated by integrin α5β1 because a monoclonal antiα5 subunit antibody could block cell adhesion to FN, whereas anti-α2 and anti-α3 antibodies had no effect on cell adhesion to FN. The divergence of α5β1 expression in these two distinct colon carcinoma phenotypes suggested that high expression of α5β1 might contribute to malignant progression in this model system. To test this hypothesis, GEO cells, a Group III cell line that did not express α5 integrin, were transfected with the α5 subunit. Stable transfection of α5 sense cDNA into a typical GEO-limiting dilution clone led to the expression of α5 subunit mRNA and cell surface α5β1 protein. The α5 sense transfectants showed enhanced attachment to FN-coated plates and were more tumorigenic when the cells were injected into athymicnude mice. These results indicate that inappropriately high α5β1 integrin expression contributes to malignant progression in colon carcinoma.
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M3 - Article
C2 - 8993837
AN - SCOPUS:0031017019
SN - 1044-9523
VL - 8
SP - 83
EP - 90
JO - Cell Growth and Differentiation
JF - Cell Growth and Differentiation
IS - 1
ER -