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The role of cell of origin and cancer stem cells in glioblastoma

日期: 2019-08-16
题目:The role of cell of origin and cancer stem cells in glioblastoma
主讲人:Luis F. Parada, PhD
Brain Tumor Center
Memorial Sloan Kettering Cancer Center
The adult mammalian brain is composed of a diversity of cell types. Using genetically engineered mouse models, we have addressed whether there exists equivalent tumorigenic potential among the diverse cell types. Our results indicate that while adult neural stem and progenitor cells harboring tumor suppressor mutations readily give rise to GBM, more differentiated neurons and glia harboring the same mutations do not create tumors. We have extended these studies to examine whether different cell lineages can give rise to tumors and find that both SVZ derived as well as oligodendrocytic lineage progenitor cells harboring identical mutations can produce GBM. However, the GBMs arising from the two different lineages exhibit subtle but distinct tumor phenotypes and harbor transcriptomes that reflect their specific cells of origin. Evidence that these two GBM subtypes are present in the human GBM data-?‐base suggest that GBM may be stratified based on cell of origin and may provide a functional premise for therapeutic evaluation. Finally, we confirm that hierarchical tumor growth originally seen in mouse models is also present in human GBM and that targeting of quiescent cancer stem cells will be essential in curing this disease.