Cell of Origin and Cancer Stem Cells in Tumor Suppressor Mouse Models of Glioblastoma.
The cellular origins and the mechanisms of progression, maintenance of tumorigenicity, and therapeutic resistance are central questions in the glioblastoma multiforme (GBM) field. Using tumor suppressor mouse models, our group recently reported two independent populations of adult GBM-initiating central nervous system progenitors. We found different functional and molecular subtypes depending on the tumor-initiating cell lineage, indicating that the cell of origin is a driver of GBM subtype diversity. Using an in vivo model, we also showed that GBM cancer stem cells (CSCs) or glioma stem cells (GSCs) contribute to resistance to chemotherapeutic agents and that genetic ablation of GSCs leads to a delay in tumor progression. These studies are consistent with the cell of origin and CSCs as critical regulators of the pathogenesis of GBM.
Brain Tumor Center and Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065.
Sheila R
SR
Alcantara Llaguno
Brain Tumor Center and Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065.
Xuanhua
X
Xie
Brain Tumor Center and Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065.
Luis F
LF
Parada
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000502:physiology*; D002490:Central Nervous System / Q000166:cytology*; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D051379:Mice; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000187:drug effects
D000970:Antineoplastic Agents