To Function, Brain Stem Cells May Rely On A Specific Molecule

The "cradle" of new neurons in the adult brain is the subventricular zone, a tissue structure lining the lateral ventricles. This is where neural or brain stem cells reside, the cells responsible for generating new neurons if needed.

For many years now, the subventricular zone has been suspected to be the origin of specific malignant brain tumors called gliomas, the most deadly type of which is glioblastoma. Now researchers have shown that brain stem cells in the subventricular zone are characterized by a specific molecule: Protein Tlx, a transcription factor, which stimulates the activity of various genes. In adult mice Tlx is expressed exclusively in brain stem cells. When the scientists switched off Tlx, there were no more detectable stem cells in the brain and the formation of new neurons ceased. Functioning of the stem cells thus appears to depend on the presence of this protein.

In the recent study the teams headed by Professor Günther Schütz and Professor Peter Lichter at the German Cancer Research Center, along with Professor Dr. Guido Reifenberger of Düsseldorf University, tested the opposite case: What happens if the production of Tlx is increased? Using a molecular-biological trick, the investigators induced an overproduction of Tlx by the brain stem cells of mice. As a result, cell division activity in the subventricular zone increased, the cells left their habitual environment called stem cell niche, and started forming glioblastoma-like tissue lesions. In another experiment in which the researchers additionally switched off the p53 protein as an important cancer brake, invasively growing glioblastomas arose from the cancer precursors.

The researchers discovered that stem cells with increased Tlx production stimulate the formation of new vessels. This enables the cells to migrate into distant brain regions and, thus, to generate the typical coral-like growth of glioblastoma.

"We recognize brain stem cells specifically by their Tlx production. If we boost it, the tissue stem cell turns into a cancer stem cell from which malignant glioblastomas arise. Therefore, we are now able, for the first time, to hold brain stem cells directly responsible for the formation of brain tumor stem cells," Günther Schütz explained.

Adapted from the Helmholtz Association of German Research Centers announcement.