Generation of a molecular interactome of the glioblastoma perivascular niche reveals Integrin Binding Sialoprotein as a key mediator of tumor cell migration

Abstract

Glioblastoma (GBM) is characterized by extensive microvascular hyperproliferation. In addition to supplying blood to the tumor, GBM vessels also provide trophic support to glioma cells and serve as conduits for migration into the surrounding brain promoting recurrence. Here, we enriched CD31-expressing glioma vascular cells (GVC) and A2B5-expressing glioma tumor cells (GTC) from primary GBM and utilized RNA sequencing to create a comprehensive interaction map of the secreted and extracellular factors elaborated by GVC that can interact with receptors and membrane molecules on GTC. To validate our findings, we utilized functional assays, including a novel hydrogel-based migration assay and in vivo mouse models to demonstrate that one identified factor, the little-studied integrin binding sialoprotein (IBSP) enhances tumor growth and promotes the migration of GTC along the vasculature. This perivascular niche interactome will serve a resource to the research community in defining the potential functions of the GBM vasculature.