title: Glycosylation of the laminin receptor (α3β1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells.
abstract: Invasion is the key requirement for cancer metastasis. Expression of β1,6 branched N-oligosaccharides associated with invasiveness, has been shown to promote adhesion to most Extra Cellular Matrix (ECM) and basement membrane (BM) components and haptotactic motility on ECM (fibronectin) but attenuate it on BM (laminin/matrigel) components. To explore the mechanism and to evaluate the significance of these observations in terms of invasion, highly invasive B16BL6 cells were compared with the parent (B16F10) cells or B16BL6 cells in which glycosylation was inhibited. We demonstrate that increased adhesion to matrix components induced secretion of MMP-9, important for invasion. Further, both the subunits of integrin receptors for fibronectin (α5β1) and laminin (α3β1) on B16BL6 cells were shown to carry these oligosaccharides. Although, glycosylation of receptors had no effect on their surface expression, it had same differential effect on cell spreading as haptotactic motility. Absence of correlation between invasiveness and expression of most tetraspanins (major regulators of integrin function) hints at an alternate mechanism. Here we show that glycosylation on α3β1 impedes its association with CD151 and modulates spreading and motility of cells apparently to reach an optimum required for invasion of BM. These studies demonstrate the complex mechanisms used by cancer cells to be invasive.
authors: Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Sector 22, Kharghar, Navi Mumbai 410210, India.
authors: Amit
authors: A
authors: Ranjan
authors: Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Sector 22, Kharghar, Navi Mumbai 410210, India.
authors: Sanjay M
authors: SM
authors: Bane
authors: Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Sector 22, Kharghar, Navi Mumbai 410210, India. Electronic address: rkalraiya@actrec.gov.in.
authors: Rajiv D
authors: RD
authors: Kalraiya
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology*; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D004338:Drug Combinations; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D039201:Integrin alpha3beta1 / Q000235:genetics / Q000378:metabolism*; D039081:Integrin alpha5beta1 / Q000235:genetics / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060185:Tetraspanin 24 / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D004338:Drug Combinations; D005353:Fibronectins; D039201:Integrin alpha3beta1; D039081:Integrin alpha5beta1; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; D017474:Receptors, Laminin; D060185:Tetraspanin 24; C059485:matrigel; D003094:Collagen; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Basement membrane; Integrin α3β1; Invasion; Metastasis; Tetraspanin CD151; β1,6 branched N-linked oligosaccharides