Gliomas account for over 80% of malignant brain tumors and current treatments have limited effect on patient outcome. Now, a new paper in Cell Reports from the lab of Dr. Steven Goldman, M.D., Ph.D., based at the University of Rochester Medical Center, identifies a several signaling pathways misregulated in glial progenitor cells (GPCs) from gliomas. These genes function in a pathway that may prove critical in tumor growth and present an attractive target for the development of new therapeutics. The group isolated GPCs from normal brain tissue and from glioma samples using a GPC marker. The glioma tumor progenitor cells (TPCs) retain the ability to produce multiple neural cell types like their GPC counterparts, express other characteristics of stem cells, and can give rise to new gliomas when transplanted into mice. Comparison of normal GPCs to TPCs revealed a number of genes that were overexpressed in the TPCs. Inactivating the transcription factor SIX1, whose expression was highly elevated in TPCs along with its cofactor, caused TPCs to stop dividing in culture and to die, and prevented TPCs from inducing new tumors in mice, identifying a potential therapeutic target. This research was a collaborative effort and included additional NYSTEM-funded scientists Dr. Abdellatif Benraiss, also at the University of Rochester, and Dr. Fraser Sim at the University at Buffalo. This work was supported in part by NYSTEM IIRP award to Dr. Goldman (C026428).
Auvergne RM, Sim FJ, Wang S, Chandler-Militello D, Burch J, Al-Fanek Y, Davis D, Benraiss A, Walter K, Achanta P, Johnson M, Quinones-Hinojosa A, Natesan S, Ford HL, Goldman SA. Transcriptional Differences between Normal and Glioma-Derived Glial Progenitor Cells Identify a Core Set of Dysregulated Genes. Cell Reports. 2013 June 27 3: 1-15.