Re-expression of the alpha 2 beta 1 integrin abrogates the malignant phenotype of breast carcinoma cells.

Zutter MM, Santoro SA, Staatz WD, Tsung YL
Proc Natl Acad Sci U S A. 1995 92 (16): 7411-5

PMID: 7638207 · PMCID: PMC41349 · DOI:10.1073/pnas.92.16.7411

To assess the role of altered alpha 2 beta 1 integrin expression in breast cancer, we expressed the alpha 2 beta 1 integrin de novo in a poorly differentiated mammary carcinoma that expressed no detectable alpha 2-integrin subunit. Expression of the alpha 2 beta 1 integrin resulted in a dramatic phenotypic alteration from a fibroblastoid, spindle-shaped, non-contact-inhibited, motile, and invasive cell to an epithelioid, polygonal-shaped, contact-inhibited, less motile, and less invasive cell. Although expression of the alpha 2 subunit did not alter adhesion to collagen, it profoundly altered cell spreading. Re-expression of the alpha 2 beta 1 integrin restored the ability to differentiate into gland-like structures in three-dimensional matrices and markedly reduced the in vivo tumorigenicity of the cells. These results indicate that the consequences of diminished alpha 2 beta 1-integrin expression in the development of breast cancer and, presumably, of other epithelial malignancies are increased tumorigenicity and loss of the differentiated epithelial phenotype.

MeSH Terms (15)

Animals Cell Adhesion Cell Differentiation Cell Division Cell Movement Female Gene Expression Integrins Mammary Neoplasms, Experimental Mice Neoplasm Invasiveness Phenotype Receptors, Collagen Transfection Tumor Cells, Cultured

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