Glycosylation of the laminin receptor (伪3尾1) regulates its association with tetraspanin CD151: Impact on cell spreading, motility, degradation and invasion of basement membrane by tumor cells

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• 作者：Amit Ranjan ; Sanjay M. Bane ; Rajiv D. Kalraiya ; ^{rkalraiya@actrec.gov.in" class="auth_mail}
• 关键词：Metastasis ; 尾1 ; 6 branched N-linked oligosaccharides ; Basement membrane ; Invasion ; Integrin 伪3尾1 ; Tetraspanin CD151
• 刊名：Experimental Cell Research
• 出版年：1 April, 2014
• 年：2014
• 卷：322
• 期：2
• 页码：249-264
• 全文大小：5961 K

文摘

Invasion is the key requirement for cancer metastasis. Expression of 尾1,6 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 (伪5尾1) and laminin (伪3尾1) 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 伪3尾1 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.