Figure 1. Heparan sulfate proteoglycan (HSPG) glycosaminoglycan side chains bind and sequester ligands in the extracellular environment.
(A) Dependent on the HSPG core protein, HSPGs are found at the cell surface, in the extracellular matrix, or in secretory vesicles. HSPG function is critical for normal growth and development and includes regulation of ligand-mediated signaling, cell adhesion, and formation of the extracellular matrix for cell migration. (B) Model for SULF2 regulated RTK signaling in glioblastoma. SULF2 acts on HSPGs, present in the tumor microenvironment, to decrease 6O-sulfation, release sequestered ligands such as PDGF and increase activation of the RTK PDGFR-alpha and downstream signaling pathways in tumor cells. RTK, receptor tyrosine kinase.