Evidence For Label-Retaining Tumor Initiating Cells In Human Glioblastoma

Individual tumor cells display diverse functional behaviors in terms of proliferation rate, cell-cell interactions, metastatic potential and sensitivity to therapy. Moreover, sequencing studies have demonstrated surprising levels of genetic diversity between individual patient tumors of the same type. Tumor heterogeneity presents a significant therapeutic challenge as diverse cell-types within a tumor can respond differently to therapies, and inter-patient heterogeneity may prevent the development of general treatments for cancer. One strategy that may help overcome tumor heterogeneity is the identification of tumor subpopulations that drive specific disease pathologies for the development of therapies targeting these clinically relevant subpopulations. Here we have identified a dye-retaining brain tumor population that displays all the hallmarks of a tumor-initiating subpopulation. Using a limiting dilution transplantation assay in immuno-compromised mice, label-retaining brain tumor cells display elevated tumor initiation properties relative to the bulk population. Importantly, tumors generated from these label-retaining cells exhibit all the pathological features of the primary disease. Together, these findings confirm dye-retaining brain tumor cells as drivers of tumor initiation and therefore viable targets for the development of therapeutics targeting this subpopulation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3324. doi:10.1158/1538-7445.AM2011-3324