Four subpopulations of B16 amelanotic melanoma cells, possessing different abilities to induce platelet aggregation (TCIPA) and to form lung colonies, were isolated by centrifugal elutriation. The expression of αIIb, α3 and α5β1 integrins was examined in the 4 subpopulations in order to determine the relationship between integrin receptor expression and tumor‐cell metastatic potential. The mRNA of αIIb, α5, β1 and β3 was detectable in the 4 subpopulations by Northern blotting. A gradual increase in mRNAs and cell‐surface immunoreactivity of the αIIbβ3 receptor, but not in their gene copies, was observed from the low to the high metastatic subpopulations. The ability of tumor cells to adhere to fibronectin and subendothelial matrix (SEM) increased in parallel. In the high metastatic cells, the αIIbβ3 receptors, but not the α5β1 receptors, were localized to focal adhesion plaques. Incubation of the high metastatic cells with αIIbβ3‐specific antibodies reduced their matrix adhesion, TCIPA and lung‐colonizing abilities. In contrast, in the low met‐ astatic cells, SEM adhesion and lung‐colony formation were not affected by anti‐αIIbβ3 antibody treatment. Incubation of either the low or the high metastatic subpopulation with an α5β1‐specific antibody had no effect in vitro and showed a slight inhibition of lung colonization in vivo. Our results suggest that several phenotypic characteristics of the enhanced metastatic potential of B16a subpopulations may be mediated by increased expression of αIIbβ3 receptors and that expression of these receptors may be regulated at the transcriptional level.
ASJC Scopus subject areas
- Cancer Research