of the Max - MDC

Figure 2. Uncoupled astrocyte from the corpus
callosum (left) and a coupled astrocyte network
in the cortex (right)
However, the effects of ATP on migration in cd39 deficient
microglia can be restored by co-stimulation with adenosine
or by addition of a soluble ectonucleotidase. We also tested
the impact of cd39 deletion in a model of ischemia, in an
entorhinal cortex lesion and in the facial nucleus after facial
nerve lesion. The accumulation of microglia at the pathological
sites was markedly decreased in cd39 deficient animals.
We conclude that the co-stimulation of purinergic and
adenosine receptors is a requirement for microglial migration
and that the expression of cd39 controls the
ATP/adenosine balance (funded by DFG).
Do microglial cells influence glioma cells?
Gliomas comprise the majority of cerebral tumors and
patients have a poor prognosis since there is essentially no
concept for successful treatment. Gliomas include astrocytomas,
oligodendrogliomas, and the most malignant (and
untreatable) brain tumor, the glioblastoma multiforme. We
study the cellular properties of these tumor cells and compare
them to normal glial cells with respect to their physiological
properties and their abilities to proliferate and
migrate. Currently, we are addressing the question as to
whether microglial cells influence tumor cell behavior. In a
slice culture, we injected a defined amount of tumor cells
and quantified their migration within tissue. We found that
microglial cell depletion from the slice slowed tumor invasion.
Thus, the presence of microglial cells promotes the
invasion of tumor cells. Our results indicate that glioma
cells change the expression pattern of microglial cells and
we can mimic this influence even in vitro using glioma-conditioned
medium. We could establish that glioma-conditioned
medium triggers the upregulation of both metalloprotease-2
and MT1-MMP, a membrane bound enzyme which
converts the inactive precursor of metalloprotease-2 into its
active form. Since metalloproteases degrade extracellular
matrix, their presence favours the invasion of glioma cells.
Thus glioma cells instruct microglial cells to help them
invade into healthy brain tissue. This research is funded by
a binational BMBF grant with Bozena Kaminska, Warsaw
(DLR 01GZ0304).
162 Function and Dysfunction of the Nervous System