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 with the degree of dermal invasiveness. Here we have studied the role the
alpha 3 integrin subunit in
malignant melanoma cell migration and invasion into extracellular matrices. The 2/14 clone of the Me665/2 human
melanoma cell line, which expresses high levels of VLA
integrins, was 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 cells, indicating a crucial role for VLA
integrins in these phenomena. While anti-alpha 6
antibodies inhibited adhesion to
laminin and anti-alpha 5
antibodies inhibited adhesion to
fibronectin,
antibodies to the alpha 3 subunit did not inhibit adhesion of these cells to
laminin,
fibronectin, or
collagen i.v. 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 anti-alpha 3 antibody, F4, did not effect migration, while both the P1B5 and F4
antibodies induced cellular aggregation on
Matrigel. Our data suggest a specific role for alpha 3 beta 1 in the migration and invasion of
melanoma cells.