THE ALPHA-3-BETA-1 INTEGRIN IS INVOLVED IN MELANOMA CELL-MIGRATION AND INVASION

The VLA3 (alpha 3 beta 1) integrin receptor recognizes several ligands ; however, the function of this integrin is still debated. Expression of VLA3 appears to be increased in malignant melanoma and correlates w ith the degree of dermal invasiveness. Here we have studied the role t he alpha 3 integrin subunit in malignant melanoma cell migration and i nvasion into extracellular matrices. The 2/14 clone of the Me665/2 hum an melanoma cell line, which expresses high levels of VLA integrins, w as highly migratory and invasive, while the low integrin expressing 2/ 56 clone showed limited migration and was not invasive. Antibodies to the beta 1 subunit inhibited adhesion, migration, and invasion of two different malignant melanoma cell lines, the 2/14 clone and A2058 cell s, indicating a crucial role for VLA integrins in these phenomena. Whi le anti-alpha 6 antibodies inhibited adhesion to laminin and anti-alph a 5 antibodies inhibited adhesion to fibronectin, antibodies to the al pha 3 subunit did not inhibit adhesion of these cells to laminin, fibr onectin, or collagen IV. In contrast, the P1B5 anti-alpha 3 antibodies were good inhibitors of the migration of these cells toward laminin, fibronectin, and collagen IV and also blocked invasion of these cells through a reconstituted basement membrane matrix (Matrigel). Another a nti-alpha 3 antibody, F4, did not effect migration, while both the P1B 5 and F4 antibodies induced cellular aggregation on Matrigel. Our data suggest a specific role for alpha 3 beta 1 in the migration and invas ion of melanoma cells. (C) 1995 Academic Press, Inc.