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The immune system not only recognizes and attacks exogenous organisms like bacteria and viruses but also prevents the body from risks arising from aberrations of its own cells like tumor growth. Research from recent years has shown that brain tumors such as glioblastoma, an especially aggressive tumor, can manipulate immune cells such as macrophages to help foster its own growth instead of destroying it. Professor Dr. Karl-Heinz Plate, head of the Neurological Institute of the Johann Wolfgang Goethe-Universität Frankfurt am Main, Germany, and his colleagues demonstrated in animal experiments that tumor growth was reduced when macrophage function was blocked, as he reported during the Brain Tumor 2006 conference of the Max Delbrueck-Center for Molecular Medicine (MDC) in Berlin-Buch and the Helios Klinikum Berlin-Buch.
Glioblastoma are tumor cells that arise as a result of uncontrolled growth of glia cells in the brain. They are the most frequent and aggressive of the brain tumors. Latest research shows that glioblastoma consist not only of mis-directed glia cells but also of up to fifty percent of macrophages, special cells of the immune system which are able to destroy tumor cells.
The central nervous system (CNS) is largely excluded from direct immune reactions. Possessing only a limited ability for regeneration, the CNS protects itself against intruding killer cells (which are also immune cells) and macrophages with a physiological barrier called the blood-brain barrier. This barrier only allows limited access of the immune cells.
Thus, researchers had assumed for a long time that the central nervous system and the immune system are completely separated. However, in recent years more and more immune cells were detected in the brain. At the same time, it became clear that the presence of immune cells in the brain does not necessarily mean that they attack tumors.
On the contrary, the function of the macrophages in the brain seems to be reversed due to signals sent out by the tumor. Rather than destroying the tumor, the macrophages secrete a growth factor called vascular endothelial growth factor (VEGF).
VEGF activates the formation of new blood vessels (angiogenesis) which, in turn, supply the tumor with nutrients and oxygen necessary for continuous growth. Apparently, it is the tumor that triggers the macrophages to secrete VEGF. The fact that almost half of a glioma consists of macrophages could possibly explain the rapid growth of glioblastoma. The VEGF receptor plays a central role for the migration of macrophages in the body toward hotspots of inflammation.
Professor Plate and his collaborators could show in mice lacking the VEGF receptor that tumor growth was considerably reduced.
The researcher hopes to be able to apply this mechanism toward a new approach in the treatment of brain tumors. In contrast to conventional therapy this treatment would aim to block the macrophages in a targeted manner parallel to destroying the tumor cells. "For patients, it might even be better if the macrophages never reach the tumor", Plate said at the conference. The future will tell whether these approaches indeed lead to an effective therapy.
Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de
http://www.mdc-berlin.de/englisch/about_the_mdc/public_relations/e_index.htm
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