1. A molecular interactome of the glioblastoma perivascular niche reveals integrin binding sialoprotein as a mediator of tumor cell migration
- Author
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Ghochani, Yasmin, Muthukrishnan, Sree Deepthi, Sohrabi, Alireza, Kawaguchi, Riki, Condro, Michael C, Bastola, Soniya, Gao, Fuying, Qin, Yue, Mottahedeh, Jack, Iruela-Arispe, M Luisa, Rao, Nagesh, Laks, Dan R, Liau, Linda M, Mathern, Gary W, Goldman, Steven A, Carmichael, S Thomas, Nakano, Ichiro, Coppola, Giovanni, Seidlits, Stephanie K, and Kornblum, Harley I
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Cancer ,Rare Diseases ,Biotechnology ,Brain Cancer ,Brain Disorders ,Neurosciences ,Animals ,Mice ,Glioblastoma ,Integrin-Binding Sialoprotein ,Brain Neoplasms ,Neoplastic Stem Cells ,Glioma ,Cell Movement ,Hydrogels ,CP: Cancer ,IBSP ,endothelial cells ,glioblastoma ,glioma ,hydrogel ,interactome ,migration ,pericytes ,perivascular niche ,stem cell ,integrins ,integrin alpha V ,integrin binding sialoprotein ,bone sialoprotein ,blood vessel ,vasculature ,glioma vasculature ,brain cancer ,glioma stem cell ,glioblastoma stem cell ,A2B5 ,RNA sequencing ,mesenchymal ,proneural ,Medical Physiology ,Biological sciences - 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.
- Published
- 2022