Elucidating the role of chondroitin sulfate glycosaminoglycans in promoting glioma cell invasion

Abstract

Glioblastoma multiforme (GBM) is the most aggressive form of astrocytoma accounting for a majority of diagnosed brain tumors in the United States. Chondroitin sulfate proteoglycans (CSPGs) and their glycosaminoglycan (GAG) side chains are essential to the brain extracellular matrix (ECM) and have been implicated in promoting glioma invasion. However, the mechanisms by which sulfated CS-GAGs promote brain tumor invasion are currently unknown. We hypothesize that glioma cell invasion is triggered by altered sulfation of CS-GAGs present in the tumor extracellular environment, and that this is potentially mediated by independent mechanisms involving CXCL12/CXCR4 and LAR signaling respectively. We designed a comprehensive in vitro study to investigate the effects of sulfated CS-GAGs in promoting the infiltration and haptotaxis of the human-derived U87MG-EGFP glioma cell line encapsulated within different hydrogel matrices. We found evidence to suggest that sulfated CS-GAGs may directly induce the enhanced invasion and haptotaxis of glioma cells associated with aggressive brain tumors.