EXPRESSION OF THE INTEGRIN ALPHA-4-BETA-1 ON MELANOMA-CELLS CAN INHIBIT THE INVASIVE STAGE OF METASTASIS FORMATION

Among a series of adhesion molecules, expression of integrin alpha 4 beta 1 showed a unique inverse correlation with the invasive potential of B16 melanoma cell lines. When an alpha 4 cDNA was introduced into an alpha 4(-)beta 1(+) highly invasive melanoma line, alpha 4 beta 1 heterodimers were expressed on the surface. Matrigel invasion by the alpha 4(+)beta 1(+) cells was reduced. Pulmonary metastasis was also suppressed when the transfectants were placed subcutaneously, but not when injected intravenously. Expression of alpha 4 beta 1 promoted homotypic intercellular adhesion. The homotypic adhesion was abrogated, and the alpha 4(+)beta 1(+) (less invasive cell lines) increased matrigel invasion following the anti-alpha 4 MAb treatment. These results suggest that integrin alpha 4 beta 1 could play a role in controlling melanoma cell metastasis at the invasive stage.