Integrin alpha2beta1 recognizes laminin-2 and induces C-erb B2 tyrosine phosphorylation in metastatic human melanoma cells.
Previous studies have shown that tumor cells with metastatic propensity secrete more of the laminin alpha2 chain than non-metastatic tumor cells do, and that laminin-2, which contains the alpha2 chain, promotes cell adhesion better than laminin-1 (Jenq et al. (1994). Differentiation, 58, 29-36). The current studies were designed to determine whether a correlation exists between the expression of the laminin-2 isoform and the metastatic phenotype in melanoma cells. We found that expression of the laminin-2 isoform was upregulated in the metastatic melanoma cell lines tested. Cell attachment studies showed that metastatic melanoma cells attached more efficiently to laminin-2 substrates. Studies on integrin expression revealed that the presence of alpha2beta1 integrin correlated with expression of the laminin-2 isoform in metastatic melanoma cells; anti-integrin alpha2 antibody prevented cell attachment to laminin-2 substrates. The data suggest that the alpha2beta1 integrin is the receptor mediating cell attachment to the laminin-2 isoform. This interaction, mediated by the alpha2beta1 integrin, stimulates secretion of the 72 kD type IV collagenase and induces a specific 185 kD protein tyrosine phosphorylation. The 185 kD tyrosine-phosphorylated protein was identified as the p185/C-erb B2 oncoprotein by immunoprecipitation. These studies suggest that upregulation of expression of the laminin-2 chain correlates with the metastatic phenotype of melanoma cells and provides evidence that the specific p185/C-erb B2 tyrosine phosphorylation may be involved in integrin-mediated signaling during tumor cell invasion and metastasis.
Han
J
J
The Connective Tissue Research Institute, Department of Medicine, University of Pennsylvania, The University City Science Center, Philadelphia 19104, USA.
Jenq
W
W
Kefalides
N A
NA
D017364:Collagenases / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D008545:Melanoma; D010641:Phenotype; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D038981:Receptors, Collagen; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
D017364:Collagenases; D016023:Integrins; D007797:Laminin; D018719:Erb-b2 Receptor Tyrosine Kinases; D038981:Receptors, Collagen; D014443:Tyrosine