Astrocytes Appear to Play an Important Role in Brain Tumors17.06.2011 - (idw) Max-Delbrück-Centrum für Molekulare Medizin (MDC) Berlin-Buch
A special group of glial cells which have the form of stars and are therefore called astroglial cells or astrocytes, seem to play a crucial role in brain tumor development and dissemination. This was pointed out by Dr. Florian Siebzehnrubl (University of Florida College of Medicine, Gainesville, USA) on Friday, June 17, 2011, at the Brain Tumor Meeting in the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany.
In his presentation, Dr. Florian Siebzehnrubl from Professor Dennis Steindlers laboratory illuminated the interaction between tumor stem cells and the extracellular matrix (ECM). The latter holds the tissue together and blocks the invasion of tumor cells. During the development of the nervous system, astrocytes form barriers mediated by the ECM. These immature astrocytes have similarities to neural stem cells.
Cells that are similar to these immature astrocytes can also play a role in brain tumors, Dr. Siebzehnrubl said. The reason is that these immature astrocytes are very similar to stem cells. Several years ago the Steindler lab was the first to discover cancer stem cells in glioblastoma, the most common and most aggressive form of brain tumors. The scientific consensus is that such tumor stem-like cells can initiate cancer and are also to blame for the fact that tumors can recur despite treatment.
The ECM plays a key role in the development and spread of brain tumors, Dr. Siebzehnrubl said, and he also presented new findings on a brain tumor cell that possesses a unique molecular profile (ZEB1) and which is involved in resistance to many current chemotherapeutics and thus involved in brain tumor recurrence.
A few years ago, the laboratory of Professor Helmut Kettenmann of the MDC in collaboration with the neurosurgeon Dr. Darko S. Markovic (Helios Klinikum Berlin-Buch) and Dr. Michael Synowitz (Charité Universitätsmedizin Berlin) showed that microglia degrade the ECM by means of specific proteases, thus enabling glioblastomas to infiltrate the brain.
In a current study using animal models, Professor Steindler and his colleagues Dr. Siebzehnrubl and Dan Silver demonstrated that tumor cells that rapidly infiltrate tissue influence the molecular composition of the ECM differently than those that are less invasive. The researchers suspect that the change in behavior of the ECM may be due to the influence of tumor stem cells.
Therefore first studies are ongoing to modulate the ECM and other cancer-associated molecules so that brain tumors are cordoned off and brain tumor-initiating cells are less migratory, thus keeping them from infiltrating healthy brain tissue.
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