Negative cooperativity between alpha 3 beta 1 and alpha 2 beta 1 integrins in human mammary carcinoma MDA MB 231 cells.
The alpha 3 beta 1 integrin has been implicated as a receptor for several matrix components, including collagen, fibronectin, and laminins. The function of alpha 3 beta 1 seems to be very versatile involving cell adhesion to or migration on ECM, establishment of cell-cell contacts in aggregates, as well as linkage to intracellular tyrosine phosphorylation cascades. Here we report a strong induction of attachment of alpha 3 beta 1 integrin expressing human breast carcinoma cell line MDA MB 231 to matrix proteins by two alpha 3 integrin subunit function-blocking monoclonal antibodies (P1B5 and ASC-1). In contrast, stimulation of adhesion to ECM by inhibitory alpha 3 integrin-specific antibodies was not observed in the alpha 3 beta 1 integrin-expressing nonmalignant human mammary epithelial cell line MCF-10A or the human breast carcinoma cell line MDA MB 468 that expressed relatively low amounts of alpha 3 beta 1 integrin at the cell surface. This increase was specific for collagens and not observed on fibronectin or laminin. Physiological concentrations of bivalent cations were not required. MAb P1B5 did not induce homotypic aggregation of MDA MB 231 cells. The P1B5-induced increase in cell attachment to collagens could be prevented but not reduced below control levels by blocking mAb to the alpha 2 integrin subunit. Function blocking anti-alpha 5 integrin subunit mAb was without effect while anti-beta 1-mAb completely abolished adhesion. Our data indicate that negative cooperativity between integrins results in transdominant inhibition of alpha 2 beta 1 function by alpha 3 beta 1 in human MDA MB 231 but not MDA MB 468 tumor cells or nonmalignant MCF-10A cells.
Lichtner
R B
RB
Research Laboratories of Schering AG, Berlin, Germany.
Howlett
A R
AR
Lerch
M
M
Xuan
J A
JA
Brink
J
J
Langton-Webster
B
B
Schneider
M R
MR
D000911:Antibodies, Monoclonal / Q000378:metabolism; D001943:Breast Neoplasms; D002413:Cations, Divalent; D002448:Cell Adhesion; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D004847:Epithelial Cells; D005260:Female; D015870:Gene Expression; D006801:Humans; D039201:Integrin alpha3beta1; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D038981:Receptors, Collagen; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002413:Cations, Divalent; D039201:Integrin alpha3beta1; D016023:Integrins; D038981:Receptors, Collagen; D003094:Collagen