title: Versatile role of heparanase in inflammation.
abstract: Heparanase is the only known mammalian endoglycosidase capable of degrading heparan sulfate glycosaminoglycan, both in extracellular space and within the cells. It is tightly implicated in cancer progression and over the past few decades significant progress has been made in elucidating the multiple functions of heparanase in malignant tumor development, neovascularization and aggressive behavior. Notably, current data show that in addition to its well characterized role in cancer, heparanase activity may represent an important determinant in the pathogenesis of several inflammatory disorders, such as inflammatory lung injury, rheumatoid arthritis and chronic colitis. Nevertheless, the precise mode of heparanase action in inflammatory reactions remains largely unclear and recent observations suggest that heparanase can either facilitate or limit inflammatory responses, when tissue/cell-specific contextual cues may dictate an outcome of heparanase action in inflammation. In this review the involvement of heparanase in modulation of inflammatory reactions is discussed through a few illustrative examples, including neuroinflammation, sepsis-associated lung injury and inflammatory bowel disease. We also discuss possible action of the enzyme in coupling inflammation and tumorigenesis in the setting of inflammation-triggered cancer.
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Goldberg
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors.forename: Amichay
authors.initials: A
authors.lastname: Meirovitz
authors.affiliation: Department of Otolaryngology, Head & Neck Surgery, Hadassah Hospital, Jerusalem 91120, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Hirshoren
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors.forename: Raanan
authors.initials: R
authors.lastname: Bulvik
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Binder
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors.forename: Ariel M
authors.initials: AM
authors.lastname: Rubinstein
authors.affiliation: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Elkin
mesh_terms: D063646:Carcinogenesis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation; D005966:Glucuronidase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D011014:Pneumonia / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D006497:Heparan Sulfate; D000099175:Heparanase