To fight the driving force of the tumor - the tumor stem cells - scientists have been trying to initiate apoptosis in these cells. However, Dr. Ana Martin-Villalba (German Cancer Research Center, DKFZ, Heidelberg, Germany) suspects that the activated apoptosis program accelerates the progress of the disease. "The tumor growth declines when apoptosis is blocked," she reported at the conference "Brain Tumor 2008" at the Max Delbrück Center (MDC) Berlin-Buch, Germany.
Glioblastomas grow like corals and form filigran branches into nearby, healthy brain tissue. For that reason it is very difficult for neurosurgeons to remove the tumor entirely because the risk of damaging healthy tissue is too high. Moreover, glioblastomas are resistant to conventional therapies which normally activate the body's apoptosis program.
This programmed cell death is a vital process. It plays an important role during development but also in the adult organism. Together with its partner CD95L, the molecular switch CD95 ensures that sick or abnormal cells are removed. Once activated, CD95 triggers a chain of different signals which in the end lead to the death of the damaged cell. Until recently, scientists were convinced that triggering apoptosis in brain tumors was a useful tool for not only killing the tumor but also the cells of its origin - the tumor stem cells.
The scientist from Heidelberg could show that CD95 as well as its partner CD95L is active in the tumor cells. However, the cells do not die. "Instead, the signal stimulates the tumor cells to migrate into neighboring, healthy brain regions," Dr. Martin-Villalba explained. For instance, it activates the protein MMP which "drills" its way into the brain tissue. "Contrary to our expectations," the neuroscientist said, "what we find when we activate apoptosis in the tumor cells is that we help them spread into healthy nerve tissue."
In experiments with mice, the researchers could already show that the tumor proliferates less aggressively when they block CD95L with an antibody, thus inhibiting the activation of programmed cell death. "With this changed perspective, we hope to develop new ideas for tumor therapy in the future," Dr. Martin-Villalba said.
Altogether, about 180 scientists and clinicians from Europe and the USA came to the two-day conference, which ended this Friday afternoon. The organizers were the MDC, the Charité - Universitätsmedizin Berlin, and HELIOS Kliniken GmbH, Berlin, a private clinic in Berlin-Buch.
Barbara Bachtler | idw
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