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

,270 people will receive a glioblastoma diagnosis in 2013 and about 14,000 people will die of the disease. Median survival is about one year.

Cell line, mouse model show something missing

"No one really knows how glioblastoma progresses from its early stages because 90-95 percent of cases are diagnosed without prior history of a lower grade glioma," Bhat said. Of these about 50 percent belong to the MES subgroup. A previous study had shown that glioblastomas with a proneural (PN) type, have a much better prognosis. But these less-aggressive tumors tend to recur as the aggressive MES subtype after treatment."

Research at MD Anderson and other institutions identified the two distinct cell types based on genes expressed by each. "We haven't known what makes a cell evolve into the MES subtype," Bhat said.

Bhat took cells from 41 human glioblastoma samples and placed them in cell cultures. Of these, 33 developed into neurospheres, cells that take on stem-cell like characteristics.

Microarray analysis of gene expression in the 17 fastest -expanding cell cultures divided them into two distinct groups: one cluster similar to the MES subtype and the other the PN subtype.

They analyzed expression of four genes commonly expressed by each subtype to see how the cultured cells matched up to their parental tumors.

Cue the surprise

All but two of the cell lines (70 percent) that originated from MES tumors lost their MES characteristics and acquired a PN signature. These results do not match the human experience, Bhat noted. Glioblastoma cells don't retreat from an aggressive to less aggressive state.

Either something in the cell culture system favored enrichment of the PN state, or most glioblastoma neurospheres exist in the less-aggressive PN state, and something in the tumor microenvironment triggers their reversible differentiation into the MES state.

Placing the
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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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