Syndecans in cancer: A review of function, expression, prognostic value, and therapeutic significance.

While our understanding of tumors and how to treat them has advanced significantly since the days of Aminopterin and the radical mastectomy, cancer remains among the leading causes of death worldwide. Despite innumerable advancements in medical technology the non-static and highly heterogeneous nature of a tumor can make characterization and treatment exceedingly difficult. Because of this complexity, the identification of new cellular constituents that can be used for diagnostic, prognostic, and therapeutic purposes is crucial in improving patient outcomes worldwide. Growing evidence has demonstrated that among the myriad of changes seen in cancer cells, the Syndecan family of proteins has been observed to undergo drastic alterations in expression. Syndecans are transmembrane heparan sulfate proteoglycans that are responsible for cell signaling, proliferation, and adhesion, and many studies have shed light on their unique involvement in both tumor progression and suppression. This review seeks to discuss Syndecan expression levels in various cancers, whether they make reliable biomarkers for detection and prognosis, and whether they may be viable targets for future cancer therapies. The conclusions drawn from the literature reviewed in this article indicate that changes in expression of Syndecan protein can have profound effects on tumor size, metastatic capability, and overall patient survival rate. Further, while data regarding the therapeutic targeting of Syndecan proteins is sparse, the available literature does demonstrate promise for their use in cancer treatment going forward.

Association between sympathoadrenal activation, fibrinolysis, and endothelial damage in septic patients: a prospective study.

PURPOSE: The purpose of this study is to investigate potential associations between sympathoadrenal activation and/or vasopressor/inotropic therapy and endothelial activation, damage, and coagulopathy in septic patients. MATERIALS AND METHODS: Septic patients included in the Scandinavian Starch for Severe Sepsis/Septic Shock trial who were expected not to receive catecholamines at screening preintervention (baseline) and had baseline blood sampled. Clinical, outcome data, and measurements of plasma concentration (p-) biomarkers reflecting sympathoadrenal activation, endothelial activation and damage, natural anticoagulation, fibrinolysis, cell damage, and platelet activation. RESULTS: Sixty-seven patients were included, of whom 14 turned out to receive noradrenaline infusion at blood sampling. These 14 patients had p-noradrenaline 5-fold higher than patients not receiving catecholamines (n=53), whereas no other baseline preintervention biomarkers differed. In the 53 patients not receiving catecholamines at blood sampling, endogenous p-noradrenaline correlated positively with adrenaline, syndecan 1, soluble vascular endothelial growth factor receptor 1, soluble CD40 ligand, tissue-type plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1) and negatively with PAI-1/tissue-type plasminogen activator ratio (all P<.05) and was independently associated with syndecan 1, soluble vascular endothelial growth factor receptor 1, and PAI-1 (all P<.05), and 28- and 90-day mortality (P<.05). CONCLUSIONS: In septic patients, endogenous noradrenaline was independently associated with biomarkers of endothelial activation, damage, fibrinolysis and mortality, comparable with findings in trauma and myocardial infarction patients. The catecholamine surge in critical illness may contribute to balance endothelial damage and procoagulation with hypocoagulability and hyperfibrinolysis in the circulating blood.