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Inflammatory protein converts glioblastoma cells into most aggressive version
Date:8/29/2013

HOUSTON -- A prominent protein activated by inflammation is the key instigator that converts glioblastoma multiforme cells to their most aggressive, untreatable form and promotes resistance to radiation therapy, an international team lead by researchers at The University of Texas MD Anderson Cancer Center reported online today in the journal Cancer Cell.

The discovery by scientists and physicians points to new ways to increase radiation effectiveness and potentially block or reverse progression of glioblastoma multiforme, the most common and lethal form of brain tumor.

"We know that the mesenchymal (MES) subgroup of glioblastoma cells is the most aggressive subgroup clinically," said co-senior author Ken Aldape, M.D., chair and professor of Pathology and Kenneth D. Muller Professor in Tumor Genetics. "This paper shows that the NF-kB pathway causes cells to change to that MES subgroup."

This conversion leads to radiation resistance.

"The pathway we identified serves as an escape mechanism for tumors," said lead author Krishna Bhat, Ph.D., assistant professor of Pathology. "In newly diagnosed patients, even before treatment, these cells already are poised to meet radiation therapy challenges."

NF-κB-driven cell change starts outside the tumor

NF-κB activation is stimulated by inflammation, which occurs in the tumor cell's microenvironment.

"The shift of tumor cells to a MES type, characterized gene expression associated with invasion and new blood vessel formation, leads to radiation resistance," said co-senior author Erik Sulman, M.D., Ph.D., assistant professor of Radiation Oncology. "This suggests blocking the inflammatory response to make tumors more sensitive to standard radiation treatment may improve outcomes for patients."

Standard care for glioblastoma is surgery, followed by radiation and chemotherapy and then treatment with temozolomide. An estimated 23
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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