Expression of the human alpha2 integrin subunit in mouse melanoma cells confers the ability to undergo collagen-directed adhesion, migration and matrix reorganization.

Previous studies have shown that cultured human and other mammalian cell require the alpha2 beta1 integrin receptor to reorganize and contract 3-dimensional extracellular matrix lattices containing collagen type I. This function is of prime importance for the later phases of wound healing, in which fibroblasts reorganize and contract extracellular matrix components newly deposited in the granulation tissue. It is also known that highly aggressive human melanoma cells have acquired this function, possibly enhancing their invasive potential. To further study alpha2 beta1-mediated functions, we expressed the human alpha2 and beta1 chains of integrins in mouse melanoma cells (BULT). The parental cell line was unable to exert known alpha2 beta1-mediated functions: The cells did not adhere, spread, or migrate on collagen type I, and they did not reorganize 3-dimensional collagen I lattices. Transfection of the human alpha2 chain was sufficient to confer not only specific adhesion to collagen type I in static adhesion assays, but also the ability to exert complex functions such as migration on collagen and efficient reorganization of collagen-I-containing matrices. Coexpression of the human beta1 chain did not further enhance these functions in BULT melanoma cells. This was underscored by the observation that alpha1-specific monoclonal antibodies were able to completely block the newly introduced functions, whereas beta1-specific antibodies had no such effect. Moreover, in transfectants expressing both the human alpha2 and beta1 chains, the human alpha2 chain did not preferentially associate with the human beta1 chain as compared with mouse beta-chains. This may indicate that the molecular structures guiding the physical association of the human alpha2 chain with beta chains are extremely highly conserved between the species.