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