Heparanase Modulates Shh and Wnt3a Signaling in Human Medulloblastoma Cells.

ABSTRACT: The pathogenesis of medulloblastoma (MB), the most common and aggressive brain tumor in children, is poorly understood. MB tumors respond to factors secreted by cerebellar Purkinje neurons such as Sonic hedgehog (Shh) and Wnt3a. Understanding the modulation of Shh/Wnt signaling is critical to developing new MB treatments. Shh and Wnt3a induce MB cell proliferation, and bind heparan sulfate glycosaminoglycan chains (HS-GAG). HS-GAG are components of syndecans: cell surface HS proteoglycans (HSPG) which act as co-receptors for extracellular matrix based ligands, and are targets of heparanase (HPSE). We hypothesized that extracellular HPSE activity can modulate MB intracellular signaling of Shh/Wnt3a, involving syndecans 1/4 carboxy terminal-associated proteins and downstream targets. We comp

SUBMITTER: Ridgway LD 

PROVIDER: S-EPMC3063606 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature