From OncoLog, November-December 2013, Vol. 58, Nos. 11-12

In Brief

NF-κB May Be Linked to Glioblastoma Treatment Resistance

NF-κB, a transcription factor associated with inflammation, and its signaling pathway may be key factors in glioblastoma aggressiveness and treatment resistance, according to new research conducted by an international group led by researchers at The University of Texas MD Anderson Cancer Center.

The research was part of an ongoing effort to identify the risk factors for and contributors to aggressiveness in glioblastoma. In this study, the researchers isolated two distinct subtypes of glioblastoma cells and showed that the more aggressive and radioresistant mesenchymal subtype of glioblastoma spontaneously converted into the less aggressive proneural subtype in cell cultures. The researchers also found that this conversion could be reversed by adding NF-κB activators to the culture medium.

Although it was previously known that cells could transition from the less aggressive proneural to the more aggressive mesenchymal subtype, the mechanism governing this transition was not known.

“The transition of tumor cells to a mesenchymal type, characterized by gene expression associated with invasion and new blood vessel formation, leads to radiation resistance,” said Erik Sulman, M.D., Ph.D., an assistant professor in the Department of Radiation Oncology and a co–senior author of the study’s report. The findings were published in September in the journal Cancer Cell.

When the researchers isolated glioblastoma cells from patients in attempts to further characterize the different types of glioblastoma cells, they found something surprising: many of the originally mesenchymal cells converted into proneural cells in cell cultures. This result was unexpected because glioblastoma almost never reverts to a less aggressive state in patients.

The unexpected findings led the team to investigate possible mechanisms for this reversion. The researchers treated proneural glioblastoma cells with tumor necrosis factor α, a cytokine that causes NF-κB signaling, and the cell cultures reliably converted into the radiation-resistant mesenchymal subtype; this effect could be reliably reversed by blocking NF-κB signaling.

This finding showed that NF-κB signaling plays an important role in the typical transformation from proneural to mesenchymal cells. According to Dr. Sulman, “These results suggest that blocking the inflammatory response to make tumors more sensitive to standard radiation treatment may improve outcomes for glioblastoma patients.”

For more information, talk to your physician, visit www.mdanderson.org, or call askMDAnderson at 877-632-6789.


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