STEM-17. SPATIAL IDENTITY OF GLIOBLASTOMA CELLS DEFINES THERAPY-INDUCED CLONAL COMPETITION. (5th November 2018)

• Record Type: Journal Article
• Authors: Ganguly, Anutosh; Yu, Hai; Ghosh, Sadashib; Komarova, Svetlana; Daisuke, Yamashita; Yamaguchi, Shinobu; Nam, Do-Hyun; Nakano, Ichiro
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi247
• Page End: vi247
• Publication Date: 2018-11-05
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy148.1024
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Glioblastoma (GBM) is characterized by high tumor heterogeneity. It has been hypothesized that the tumor core is enriched with tumor cells harboring mesenchymal phenotype, whereas the tumor edge retains those with proneural phenotype. Recent studies including ours have identified the mutually-distinct glioma stem cells (GSCs) are present in these two lesions. Here, in order to investigate the diversity of GSCs, we established subclones of GSCs from the edge and core region of the tumor of GBM patients. These subclones were then stably labeled by fluorescent proteins by a lentiviral transduction system. When either edge derived, or core derived subclones were mixed together, growth competition was observed between those subpopulations. In contrast, edge derived subclones were mixed with those from the core derived ones, the relative proportion of each remain unchanged. This data indicate that clonal competition could be dependent on the spatial identity of the original clones. Interestingly, a further shift in the competition was observed when these clones are exposed to temozolomide in the mixed cultures. In addition, the clonal competition was dependent on the ability of proliferation but not on the cell death. Selective apoptosis of non-competing clones was non-significant but were not ruled out. We will further determine the genetic and epigenetic signatures of the dominant and hyper-proliferative subclones in the mixed culture. Currently, in vivo validation of these studies are underway. Our study indicates that understanding spatial heterogeneity at the clonal level will be a crucial step to devise a new strategy for the future treatment.