International Conference on Neuro Oncology and Brain Tumor
University of Texas, M.D. Anderson Cancer Center
Title: cancer stem cells were identified as distinct subtypes with their individual progenies
In glioblastoma (GBM), Proneural (PN) and Mesenchymal (MES) cancer stem cells (CSCs) were identified as distinct subtypes with their individual progenies (non-CSCs). Here we report that following irradiation, intercellular extrinsic signals from senescent non-CSCs provoke PN CSCs’ compensatory growth, thereby resulting in persistent transcriptomic and phenotypic transformation toward more malignant MES CSCs (PN-MES transition: PMT). PMT of CSCs is accompanied with the activated wound healing pathway, which is significantly associated with poorer prognosis of GBM patients. During PMT of CSCs, a CSC marker CD133 is lost, while CDX expression evolves. These CDX-positive, but not CDX-negative GBM cells are highly tumorigenic and multipotent in vivo, suggesting CDX as a novel MES CSC marker. Inhibition of CDX attenuates clonogenicity and radioresistance. Lastly, CDX and CD133 expressions are independently instructive for poorer prognosis of MES and PN GBM, respectively. Together, irradiation to GBM tumors induces damaged non-CSC-driven PMT of CSCs developing a malignant phenotype, and CDX is a clinically relevant functional marker for MES GBM stemness.