Molecular functions of syndecan-1 in disease

Abstract

Syndecan-1 is a cell surface heparan sulfate proteoglycan that binds to many mediators of disease pathogenesis. Through these molecular interactions, syndecan-1 can modulate leukocyte recruitment, cancer cell proliferation and invasion, angiogenesis, microbial attachment and entry, host defense mechanisms, and matrix remodeling. The significance of syndecan-1 interactions in disease is underscored by the striking pathological phenotypes seen in the syndecan-1 null mice when they are challenged with disease-instigating agents or conditions. This review discusses the key molecular functions of syndecan-1 in modulating the onset, progression, and resolution of inflammatory diseases, cancer, and infection.

Is Endothelial Nitric Oxide Synthase a Moonlighting Protein Whose Day Job is Cholesterol Sulfate Synthesis? Implications for Cholesterol Transport, Diabetes and Cardiovascular Disease

“…Syndecan shedding-the release of syndecan from the cell membrane into the interstitial spaces-is well-established as a pathological response associated with inflammation, microbial infection, and cancer [133,[138][139][140]. High levels of shed syndecans in the blood plasma correlate with poor outcome in cancer patients [141,142].…”

Syndecan-1 and Its Expanding List of Contacts

“…3 Following our report, sdc1-null mice on two different genetic backgrounds (BALB/cJ and C57BL6J) have been widely used by numerous groups. 4 The purpose of this review is to describe the relevance of sdc1 in epithelial homeostasis and wound repair. Sdc1 shares structural domains with 3 additional family members called sdc2-4 and as a result, data obtained studying one sdc family member often apply to all four.…”

2-O-Sulfated Domains in Syndecan-1 Heparan Sulfate Inhibit Neutrophil Cathelicidin and Promote Staphylococcus aureus Corneal Infection

“…Many microbial pathogens, including viruses, bacteria, and parasites, are thought to exploit the heparan sulfate (HS) 2 moiety of HS proteoglycans (HSPGs) to infect host cells and to evade immune mechanisms (8,9). HSPGs are expressed ubiquitously on the cell surface and in the extracellular matrix.…”

“…HSPGs are comprised of one or several HS chains attached covalently to specific core proteins (10). HS binds to and regulates many molecules that have been implicated in the host defense against infectious agents, including cytokines, chemokines, and cationic antimicrobial factors (8,9).…”

“…Syndecan-1 is the predominant HSPG of epithelial cells, a cell type that most bacteria first encounter during their pathogenesis (8). S. aureus (16), P. aeruginosa (17), and S. pneumoniae (18) induce the shedding of syndecan-1 ectodomains from the cell surface through specific virulence factors in cultured epithelial cells.…”