title: Aberrant glycosylation of αvβ3 integrin is associated with melanoma progression.
abstract: N-glycosylation of integrins plays an important role in cancer progression. Increased αvβ3 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 αvβ3 glycosylation. Lectin precipitation, enzyme digestion and the use of swainsonine (SW) showed that αvβ3 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 αvβ3 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 αvβ3 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 αvβ3 integrin glycosylation and that both αvβ3 and β1-6-branched sialylated complex-type N-glycans promote metastatic melanoma migration on VN.
authors: Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Krakow, Poland ewa.pochec@uj.edu.pl.
authors: Ewa
authors: E
authors: Pocheć
authors: Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Krakow, Poland.
authors: Monika
authors: M
authors: Bubka
authors: Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Krakow, Poland.
authors: Magdalena
authors: M
authors: Rydlewska
authors: Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Krakow, Poland.
authors: Marcelina
authors: M
authors: Janik
authors: Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Krakow, Poland Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
authors: Małgorzata
authors: M
authors: Pokrywka
authors: Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Krakow, Poland.
authors: Anna
authors: A
authors: Lityńska
mesh_terms: D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D018450:Disease Progression; D006031:Glycosylation; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D019096:Vitronectin / Q000008:administration & dosage
chemical_list: D039302:Integrin alphaVbeta3; D019096:Vitronectin; D019158:N-Acetylneuraminic Acid
keywords: glycosylation; melanoma; migration; vitronectin; αvβ3 integrin