Abstract 2518: Crosstalk between stem and non-stem cells in glioblastoma promotes radioresistance in a CD109-dependent manner

Abstract

Glioblastoma (GBM) is a lethal brain tumor that contains cancer stem cells that are bestowed with tumor initiating and treatment resistant properties. Patient-derived glioma stem-like cells (GSCs) that resemble the clinically relevant MES subtype harbor more aggressive and therapy resistant properties. Here we report that exposure of GSCs to ionizing radiation (IR) provokes inter-cellular signals from therapy-induced senescent non-stem cancer cells to stimulate compensatory growth in cancer stem cells resulting in persistent transcriptomic and phenotypic shift toward a more MES subtype. This IR-induced gain of MES features in GSCs is accompanied by conversion of CD133+ stem cell populations to CD133- /CD109+ cells. In both de novo and IR-induced MES GSCs, CD109+, but not CD109- populations are highly tumorigenic and multipotent in vivo. Inhibition of CD109 attenuates clonogenicity and radioresistance in MES GSCs GBM. Clinically, CD109 expression is significantly associated with the MES GBMs and poorer prognosis of GBM patients. Taken together, our data imply that radiation of GSCs induces direct transformation of cancer stem cells to the MES subtype accompanied by a loss of the widely adopted stem cell marker CD133 and a gain of a novel, tumor propagating, and clinically relevant MES stem cell marker, CD109. Citation Format: Mutsuko Minata, Ichiro Nakano, Sunghak Kim, Marat PavliuKov, Jia Wang, Svetlana Komarova, Jun Wang. Crosstalk between stem and non-stem cells in glioblastoma promotes radioresistance in a CD109-dependent manner. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2518.