Glycosylation profile of integrin α 3β 1 changes with melanoma progression

Abstract

Glycosylation of integrins has been implicated in the modulation of their function. Characterisation of carbohydrate moieties of α 3 and β 1 subunits from non-metastatic (WM35) and metastatic (A375) human melanoma cell lines was carried out on peptide- N-glycosidase F-released glycans using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). β 1 integrin subunit from both cell lines displayed tri- and tetraantennary oligosaccharides complex type glycans, but only in A375 cell line was the sialylated tetraantennary complex type glycan (Hex 7HexNAc 6FucSia 4) present. In contrast, only α 3 subunit from metastatic cells possessed β1–6 branched structures. Our data indicate that the β 1 and α 3 subunits expressed by the metastatic A375 cell line carry β1–6 branched structures, suggesting that these cancer-associated glycan chains may modulate tumor cell adhesion by affecting the ligand binding properties of α 3β 1 integrin. In direct ligand binding assays, α 3β 1 integrin from both cell lines binds strongly to fibronectin and to much lesser degree to placental laminin. No binding to collagen IV was observed. Enzymatic removal of sialic acid residues from purified α 3β 1 integrin stimulates its adhesion to all examined ECM proteins. Our data suggest that the glycosylation profile of α 3β 1 integrin in human melanoma cells correlates with the acquisition of invasive capacity during melanoma progression.