title: Mechanisms of heparanase inhibitors in cancer therapy.
abstract: Heparanase is an endo-β-D-glucuronidase capable of cleaving heparan sulfate side chains contributing to breakdown of the extracellular matrix. Increased expression of heparanase has been observed in numerous malignancies and is associated with a poor prognosis. It has generated significant interest as a potential antineoplastic target because of the multiple roles it plays in tumor growth and metastasis. The protumorigenic effects of heparanase are enhanced by the release of heparan sulfate side chains, with subsequent increase in bioactive fragments and cytokine levels that promote tumor invasion, angiogenesis, and metastasis. Preclinical experiments have found heparanase inhibitors to substantially reduce tumor growth and metastasis, leading to clinical trials with heparan sulfate mimetics. In this review, we examine the role of heparanase in tumor biology and its interaction with heparan surface proteoglycans, specifically syndecan-1, as well as the mechanism of action for heparanase inhibitors developed as antineoplastic therapeutics.
authors: Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University, Durham, North Carolina, USA.
authors: Benjamin
authors: B
authors: Heyman
authors: Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University, Durham, North Carolina, USA; Department of Immunology, Duke University, Durham, North Carolina, USA. Electronic address: yang0029@mc.duke.edu.
authors: Yiping
authors: Y
authors: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D019496:Cancer Vaccines; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D005109:Extracellular Matrix / Q000378:metabolism; D015870:Gene Expression; D005966:Glucuronidase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D053668:Syndecan-1 / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D000099175:Heparanase
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D004791:Enzyme Inhibitors; D005966:Glucuronidase; D006497:Heparan Sulfate; D053668:Syndecan-1; D000099175:Heparanase