Ohio scientists block chromatin-modifying enzyme, suppressing glioblastoma growth


Scientists from Ohio State University Comprehensive Cancer Center have identified a new player in the growth of an aggressive brain tumor, or glioblastoma. The group showed that targeting a particular enzyme in the laboratory prevents cancer growth and may hold promise for the development of a new clinical treatment for glioblastoma.

Balveen Kaur and her team published their work in the journal Oncogene.

Glioblastoma (GB) resists most conventional chemotherapy and is associated with an extremely poor outcome after the initial diagnosis. Kaur and her team show that by knocking down an enzyme called PRMT5 (protein arginine methyltransferase 5), they can push the cells into senescence and reduce the growth of the cancer.

"Our findings show that inhibiting PRMT5 can affect both mature and immature tumor cells in glioblastoma, and they underscore the importance of developing PRMT5 inhibitors as a promising therapeutic approach for patients with these tumors," Kaur, a professor and vice chair of research in the Department of Neurological Surgery at Ohio State, said in a statement.

PRMT5 is a chromatin-modifying enzyme since it directly adds methyl groups to the tightly wound DNA that forms chromatin in the cell nucleus. If PRMT5 is overexpressed in GB cells the growth of the cancer is increased; this is thought to occur via certain gene expression altered by the addition of the methyl marks. 

Using a mouse model of GB and taking primary tumor cells from patients the researchers made some observations. By reducing PRMT5 expression in differentiated primary tumor cells they could cause cell death by apoptosis; in undifferentiated cells however, this led to cell-cycle arrest and senescence. In undifferentiated cells PRMT5 reduced the PTEN tumor-suppressor gene leading to cell proliferation--a finding that was not observed in differentiated cells.

GB tumor are composed of a mixed bag of undifferentiated, immature and cancer stem cells that resist treatment and differentiated cells that respond well to treatment. The finding that PRMT5 plays a different role in these cell types gives a new therapeutic angle--in a form of cancer that is currently lacking effective treatment.

- here’s the release