Aberrant Glycosylation of α_vβ₃ Integrin is Associated with Melanoma Progression

Abstract

N-glycosylation of integrins plays an important role in cancer progression. Increased α_vβ₃ integrin expression during melanoma progression is well-documented but the role of its glycans in tumorigenesis is still poorly understood. In the present study we used the WM793 primary melanoma cell line and its highly metastatic variant, WM1205Lu, to examine α_vβ₃ glycosylation. Lectin precipitation, enzyme digestion and the use of swainsonine (SW) showed that α_vβ₃ integrin glycosylation differs significantly between primary and metastatic melanoma cells. High-mannose structures and complex glycans with bisecting N-acetylglucosamine (GlcNAc) were more abundant in both subunits of primary cells. We also observed a shift in the sialylation of α_vβ₃ integrin related to reduction of α2-6-linked sialic acid expression and an increase of α2-3 sialylation of both subunits in melanoma progression. Metastatic melanoma migration on vitronectin (VN) was reduced in the presence of antibody against α_vβ₃ and the lectins phytohemagglutinin-L (PHA-L), Sambucus nigra agglutinin (SNA) and Maackia amurensis (MAA) in woundhealing assays. Our results show that the acquisition of metastatic competence by melanoma cells is accompanied by alteration of α_vβ₃ integrin glycosylation and that both α_vβ₃ and β1-6-branched sialylated complex-type N-glycans promote metastatic melanoma migration on VN.