A molecular interactome of the glioblastoma perivascular niche reveals integrin binding sialoprotein as a mediator of tumor cell migration

胶质母细胞瘤血管周围微环境的分子相互作用组揭示整合素结合涎蛋白作为肿瘤细胞迁移的介质

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作者:Yasmin Ghochani, Sree Deepthi Muthukrishnan, Alireza Sohrabi, Riki Kawaguchi, Michael C Condro, Soniya Bastola, Fuying Gao, Yue Qin, Jack Mottahedeh, M Luisa Iruela-Arispe, Nagesh Rao, Dan R Laks, Linda M Liau, Gary W Mathern, Steven A Goldman, S Thomas Carmichael, Ichiro Nakano, Giovanni Coppola, S

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 enrich CD31-expressing glioma vascular cells (GVCs) and A2B5-expressing glioma tumor cells (GTCs) from primary GBM and use RNA sequencing to create a comprehensive molecular interaction map of the secreted and extracellular factors elaborated by GVCs that can interact with receptors and membrane molecules on GTCs. To validate our findings, we utilize functional assays, including a 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 GTCs along the vasculature. This perivascular niche interactome will serve as a resource to the research community in defining the potential functions of the GBM vasculature.

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