Upregulation of alpha and beta integrin subunits in metastatic macrophage–melanoma fusion hybrids

Abstract

Fusion of cancer cells with migratory bone-marrow-derived cells such as macrophages can produce cancer cells with increased metastatic potential. To study this, we fused mouse macrophages with weakly metastatic mouse melanoma cells and generated a panel of hybrid clones. About half of these showed increased metastatic potential in mice. These hybrids expressed traits and molecules that were known indicators of tumor progression in melanoma (chemotaxis toward fibronectin, melanogenesis, autophagy, cMet, MCR1, SPARC, cell surface LAMP-1, GnT-V and β1,6-branched oligosaccharides). Here, we investigated integrin subunit expression in selected hybrids. Integrins, especially those that are substrates for the glycosyltransferase GnT-V and carriers of β1,6-branched oligosaccharides, play an important role in cell migration. We report increased expression of the integrin subunits α3, α5, α6, αv, β1, and β3 in metastatic hybrids compared with parental melanoma cells and a weakly metastatic hybrid. Notably, each of these subunits is also a substrate for GnT-V. Integrin subunit expression was further increased by inducers of cyclic AMP. Expression of these integrin subunits is a characteristic of macrophages and also associated with progression in melanoma and other cancers. In summary, our studies of macrophage-melanoma hybrids show that several α and β integrin subunits are upregulated in the metastatic lines. This adds further support for the theory that generation of a metastatic phenotype may be initiated through a single event: fusion of migratory bone marrow-derived cells with cancer cells.