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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.
AuthorsEwa Pocheć, Monika Bubka, Magdalena Rydlewska, Marcelina Janik, Małgorzata Pokrywka, Anna Lityńska
JournalAnticancer research (Anticancer Res) Vol. 35 Issue 4 Pg. 2093-103 (Apr 2015) ISSN: 1791-7530 [Electronic] Greece
PMID25862865 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
Chemical References
  • Integrin alphaVbeta3
  • Vitronectin
  • N-Acetylneuraminic Acid
Topics
  • Cell Adhesion (genetics)
  • Cell Line, Tumor
  • Cell Movement (drug effects)
  • Disease Progression
  • Glycosylation
  • Humans
  • Integrin alphaVbeta3 (genetics, metabolism)
  • Melanoma (metabolism, pathology)
  • N-Acetylneuraminic Acid (metabolism)
  • Vitronectin (administration & dosage)

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