Abstract 2297: The evidence of glioblastoma heterogenity.

Abstract

Abstract Gliomas are composed of heterogeneous combinations of cells, with different phenotypic characteristics and different proliferative potentials; however, there is no convincing evidence that only the single glioma stem cells (GSC) could be representative of patient tumor and which cell type were the root for tumor growth. Because most tumors have a clonal origin, GSCs must give rise to phenotypically diverse progenies, including matured GSCs with indefinite self-renewing potential, as well as differentiated cancer cells with limited proliferative potential. To investigate the cellular origin of population diversity, we established 4 subclones from a glioblastoma patient. These subclones were subsequently propagated and analyzed. All clones expressed stem cell makers (nestin, sox2, musashi) heterogeneously. The morphology, self-renewal and proliferative capacities of the subclones were varying. FACS and cDNA microarray analysis showed that each subclones were composed of distinct population of cells. The sensitivities of some drug were different. In animal models, xenografts from subclones, tumor-progression/invasion and animal survivals were also different. Some clones invaded contra-lateral hemisphere via tract fiber. Our observations suggest that single cell derived subclones from a patient is capable of producing phenotypically heterogeneous self-renewing progenies in an in vitro and in vivo setting. The functional analysis of the heterogeneous GSC clones may provide a better understanding of GSC biology and novel means for testing of new treatment strategies that focus on the eradication of the true GSCs. Citation Format: Akio Soeda, Akira Hara, Takahiro Kunisada, Toru Iwama. The evidence of glioblastoma heterogenity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2297. doi:10.1158/1538-7445.AM2013-2297