The syndecan-1 ectodomain regulates alphavbeta3 integrin activity in human mammary carcinoma cells.
The alpha(v)beta(3) integrin participates in cell morphogenesis, growth factor signaling, and cell survival. Activation of the integrin is central to these processes and is influenced by specific ECM components, which engage both integrins and syndecans. This paper demonstrates that the alpha(v)beta(3) integrin and syndecan-1 (S1) are functionally coupled. The integrin is dependent on the syndecan to become activated and to mediate signals required for MDA-MB-231 and MDA-MB-435 human mammary carcinoma cell spreading on vitronectin or S1-specific antibody. Coupling of the syndecan to alpha(v)beta(3) requires the S1 ectodomain (ED), as ectopic expression of glycosylphosphatidylinositol-linked S1ED enhances alpha(v)beta(3) recognition of vitronectin; and treatments that target this domain, including competition with recombinant S1ED protein or anti-S1ED antibodies, mutation of the S1ED, or down-regulation of S1 expression by small-interfering RNAs, disrupt alpha(v)beta(3)-dependent cell spreading and migration. Thus, S1 is likely to be a critical regulator of many cellular behaviors that depend on activated alpha(v)beta(3) integrins.
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
DeannaLee M
DM
Beauvais
Brandon J
BJ
Burbach
Alan C
AC
Rapraeger
D001943:Breast Neoplasms / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D002469:Cell Separation; D002470:Cell Survival; D005434:Flow Cytometry; D017353:Gene Deletion; D017261:Glycosylphosphatidylinositols / Q000737:chemistry; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000276:immunology; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction; D053668:Syndecan-1; D053667:Syndecans; D019096:Vitronectin / Q000378:metabolism
D017261:Glycosylphosphatidylinositols; D039302:Integrin alphaVbeta3; D016023:Integrins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D019096:Vitronectin; C081763:sarcoma-associated antigen S1