title: Heparanase regulation of cancer, autophagy and inflammation: new mechanisms and targets for therapy.
abstract: Because of its impact on multiple biological pathways, heparanase has emerged as a major regulator of cancer, inflammation and other disease processes. Heparanase accomplishes this by degrading heparan sulfate which regulates the abundance and location of heparin-binding growth factors thereby influencing multiple signaling pathways that control gene expression, syndecan shedding and cell behavior. In addition, heparanase can act via nonenzymatic mechanisms that directly activate signaling at the cell surface. Clinical trials testing heparanase inhibitors as anticancer therapeutics are showing early signs of efficacy in patients further emphasizing the biological importance of this enzyme. This review focuses on recent developments in the field of heparanase regulation of cancer and inflammation, including the impact of heparanase on exosomes and autophagy, and novel mechanisms whereby heparanase regulates tumor metastasis, angiogenesis and chemoresistance. In addition, the ongoing development of heparanase inhibitors and their potential for treating cancer and inflammation are discussed.
authors.affiliation: Department of Pathology, Comprehensive Cancer Center, University of Alabama at Birmingham, AL, USA.
authors.forename: Ralph D
authors.initials: RD
authors.lastname: Sanderson
authors.affiliation: Sharett Oncology Institute, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Elkin
authors.affiliation: Department of Human Oncology, Wisconsin Institutes for Medical Research, Carbone Cancer Center, University of Wisconsin-Madison, WI, USA.
authors.forename: Alan C
authors.initials: AC
authors.lastname: Rapraeger
authors.affiliation: Cancer and Vascular Biology Research Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Neta
authors.initials: N
authors.lastname: Ilan
authors.affiliation: Cancer and Vascular Biology Research Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001343:Autophagy; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D055354:Exosomes / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D015398:Signal Transduction; D053667:Syndecans / Q000235:genetics* / Q000378:metabolism; D000099175:Heparanase
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005966:Glucuronidase; D006497:Heparan Sulfate; D053667:Syndecans; D000099175:Heparanase
keywords: angiogenesis; autophagy; cancer; exosomes; heparan sulfate; heparanase; heparanase inhibitors; inflammation; metastasis; proteoglycan