List of communications


Disparate radiation response of slow proliferating glioblastoma initiating cells

Deleyrolle LP, University of Florida Dept Neurosurgery; Nabilsi N, University of Florida Dept Molecular Biology; Pasternack N, University of Florida Dept Neurosurgery; Rohaus M, University of Florida Dept Neurosurgery; Griffith B, University of Florida Dept Neurosurgery; Harding A, Translational Research Institute, Princess Alexandra Hospital, Queensland, Australia; Kladde MP, University of Florida Dept Molecular Biology; Reynolds BA, University of Florida Dept Neurosurgery; Steindler DA, University of Florida Dept Neurosurgery; Siebzehnrubl FA, Cardiff University


Glioblastoma remains the most frequent and lethal of all adult brain tumors. Recurrence after radio- and chemotherapy particularly contributes to poor outcome. Cancer stem cells have been identified as a cellular source that is more resistant to anti-cancer therapy and capable of initiating new tumor growth. We have previously shown that isolating slow proliferating cells from glioblastoma enriches for a population with cancer stem cell properties. Here, we demonstrate that these slow proliferating cancer stem cells are more chemoresistant and invasive than the rest of the tumor population, but surprisingly slow proliferating cells are more sensitive to radiation damage. We find a significant overlap between the slow proliferating compartment and expression of the transcription factor ZEB1, which we have recently identified as a master regulator of stemness and chemoresistance in glioblastoma. Consequently, ZEB1-positive cells also exhibit greater radiosensitivity. Slow proliferating, ZEB1-positive cells accumulate genomic aberrations that result in G2/M retention of these cells, rendering them more sensitive to radiation damage. However, a fraction of cells that survive irradiation respond with a rebound proliferative burst that may result in recurrence of more aggressive tumors. This disparate effect of radiation on cancer stem cells points to a previously underappreciated heterogeneity within the cancer stem cell compartment and may open up new avenues of studying and targeting specific cancer stem cell sub-populations.

Format: Poster

Organized by