Expression of the integrin α4β1 on melanoma cells can inhibit the invasive stage of metastasis formation

Abstract

Among a series of adhesion molecules, expression of integrin α4β1 showed a unique inverse correlation with the invasive potential of B16 melanoma cell lines. When an α4 cDNA was introduced into an α4 −β1 + highly invasive melanoma line, α4β1 heterodimers were expressed on the surface. Matrigel invasion by the α4 +β1 + cells was reduced. Pulmonary metastasis was also suppressed when the transfectants were placed subcutaneously, but not when injected intravenously. Expression of α4β1 promoted homotypic intercellular adhesion. The homotypic adhesion was abrogated, and the α4 +β1 + (less invasive cell lines) increased matrigel invasion following the anti-α4 MAb treatment. These results suggest that integrin α4β1 could play a role in controlling melanoma cell metastasis at the invasive stage.