Re-expression of the alpha 2 beta 1 integrin abrogates the malignant phenotype of breast carcinoma cells.
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.
Zutter
M M
MM
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Santoro
S A
SA
Staatz
W D
WD
Tsung
Y L
YL
D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement; D005260:Female; D015870:Gene Expression; D016023:Integrins / Q000235:genetics* / Q000502:physiology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness; D010641:Phenotype; D038981:Receptors, Collagen; D014162:Transfection; D014407:Tumor Cells, Cultured
D016023:Integrins; D038981:Receptors, Collagen