MGH Findings Suggest Novel Treatment Approach For Brain Tumors
A team of investigators from the Massachusetts General Hospital (MGH) has identified four transcription factors characterizing the small proportion of glioblastoma cells behind the aggressiveness and treatment resistance of the brain tumor. The team’s findings suggest a novel approach to treating glioblastoma stem cells.
The researchers identified a combination of four transcription factors (POU3F2, SOX2, SALL2 and OLIG2) able to reprogram differentiated tumor cells back into glioblastoma stem cells in vitro as well as in an animal model. The team confirmed that the four factors and their corresponding regulatory elements were active in from 2 to 7 percent of human glioblastoma cells, which also expressed a known stem cell marker.
Dr. Mario Suvà of the MGH Department of Pathology and Center for Cancer Research, and co-lead author, said, “We have identified a code of ‘molecular switches’ that control a very aggressive subpopulation of brain cancer cells, so-called glioblastoma stem cells. Understanding what drives these aggressive cells will give us insights into alternative ways of eliminating them and potentially changing the course of this very deadly tumor.”
Findings show that inhibition of a crucial regulatory protein complex’s action involving a known target gene of one of the core transcription factors caused glioblastoma stem cells to lose their stem-like properties and eventually die.
Dr. Bradley Bernstein of the MGH Pathology and the MGH Cancer Center, and senior author of the study, said, “This study brings us back to the fundamental idea that there are many reasons that cancer cells can be aggressive. Just as normal cells with the same genome differentiate into many different cell types, a single tumor characterized by specific genetic mutations can contain many different types of cells – stem-like and more differentiated cells – with the difference being rooted in their epigenetic information. Identifying the drivers of these different cellular states in glioblastoma stem cells could offer us the best opportunity for treating what remains an extremely difficult-to -treat tumor.”
The MGH team’s findings will be published in the April 24 issue of Cell and will receive an advance online release.