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

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-08, Vol.92 (16), p.7411-7415
• Main Authors: Zutter, M M, Santoro, S A, Staatz, W D, Tsung, Y L
• Format: Article
• Language: English
• Subjects: Animals; Cell Adhesion; Cell Differentiation; Cell Division; Cell Movement; Female; Gene Expression; Integrins - genetics; Integrins - physiology; Mammary Neoplasms, Experimental - genetics; Mammary Neoplasms, Experimental - pathology; Mice; Neoplasm Invasiveness; Phenotype; Receptors, Collagen; Transfection; Tumor Cells, Cultured
• ISSN: 0027-8424; 1091-6490
• 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.