Despite intense efforts in basic research and clinical medicine, glioblastoma (GBM) remains one of the most lethal types of cancer. In particular, tumor recurrence after surgical resection, aggressive chemotherapy, and targeted radiation remains an insurmountable obstacle. Recurrence may be attributed to residual cancer stem cells that re-initiate tumor growth after primary clinical intervention. Here, we provide new evidence for a subpopulation of relatively quiescent and chemoresistant cancer stem cells that invade deeply into the parenchyma. We have identified a critical transcription factor that is upregulated in these glioma stem cells, which regulates epithelial-mesenchymal transition (EMT) in other tumors. Knockdown of this transcription factor results in an increased sensitivity to chemotherapeutic agents and reduced tumor cell invasion. We hypothesize that single cell invasion of malignant gliomas is regulated by similar molecular pathways as EMT and metastasis in solid tissue tumors. These pathways allow slowly proliferating glioma stem cells to leave the site of the primary tumor, invade deeply into the surrounding parenchyma and, by virtue of their resistance to chemotherapeutic agents, evade all types of classical brain tumor therapy. This offers a potential novel model for GBM recurrence, and a potential new therapeutic target.

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 3317. doi:10.1158/1538-7445.AM2011-3317