The Good and Bad Sides of Heparanase-1 and Heparanase-2.
Adv Exp Med Biol
; 1221: 821-845, 2020.
Article
en En
| MEDLINE
| ID: mdl-32274740
In this chapter, we will emphasize the importance of heparan sulfate proteoglycans (HSPG) in controlling various physiological and pathological molecular mechanisms and discuss how the heparanase enzyme can modulate the effects triggered by HSPG. Additionally, we will also navigate about the existing knowledge of the possible role of heparanase-2 in biological events. Heparan sulfate is widely distributed and evolutionarily conserved, evidencing its vital importance in cell development and functions such as cell proliferation, migration, adhesion, differentiation, and angiogenesis. During remodeling of the extracellular matrix, the breakdown of heparan sulfate by heparanase results in the release of molecules containing anchored glycosaminoglycan chains of great interest in heparanase-mediated cell signaling pathways in various physiological states, tumor development, inflammation, and other diseases. Taken together, it appears that heparanase plays a key role in the maintenance of the pathology of cancer and inflammatory diseases and is a potential target for anti-cancer therapies. Therefore, heparanase inhibitors are currently being examined in clinical trials as novel cancer therapeutics. Heparanase-2 has no enzymatic activity, displays higher affinity for heparan sulfate and the coding region alignment shows 40% identity with the heparanase gene. Heparanase-2 plays an important role in embryogenic development however its mode of action and biological function remain to be elucidated. Heparanase-2 functions as an inhibitor of the heparanase-1 enzyme and also inhibits neovascularization mediated by VEGF. The HPSE2 gene is repressed by the Polycomb complex, together suggesting a role as a tumor suppressor.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Glucuronidasa
Límite:
Humans
Idioma:
En
Revista:
Adv Exp Med Biol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Brasil
Pais de publicación:
Estados Unidos