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In their latest research, scientists of the Max Delbrück
Center for Molecular Medicine (MDC) Berlin-Buch,
Germany, have demonstrated how the brain’s own
stem cells and precursor cells control the growth of
glioblastomas. Of all brain tumors, glioblastomas are
among the most common and most aggressive. Dr.
Sridhar Reddy Chirasani, Professor Helmut Kettenmann
and Dr. Rainer Glass (all MDC) and Dr. Michael
Synowitz (Charité – Universitätsmedizin Berlin) have
now shown in cell culture and mouse model
experiments just how the body’s own protective
mechanism they identified in an earlier study, actually
works (Brain, July 6, 2010).
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Glioblastomas are brain tumors that are most common
in adults in their mid-fifties or early sixties. The causes
for developing the disease are not yet known. Researchers
assume that misdirected neural stem cells / precursor cells
mutate into cancer cells and can form glioblastomas.
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Several years ago the MDC and Charité researchers were
able to show that normal stem cell/ precursor cells of the
brain attack the tumor. Apparently, the tumor itself entices
these stem cells to migrate over relatively long distances
from the stem cell niches of the brain. Why this is so is
unclear. Moreover, the researchers still do not know which
substance attract the stem cells to the tumor. However,
now they have discovered how the stem cells keep the
tumor in check.
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Stem cell protein induces signaling in glioblastoma cells
The scientists showed that the neural stem cells and
neural precursor cells release a protein that belongs to
the family of the BMP proteins (bone morphogenetic
protein). This protein received its name for its ability to
induce bone and cartilage tissue formation, the first
characteristic that was known about it. However, BMP
is active in the entire organism – even in the brain.
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Neural stem cells release BMP-7 in the brain in the
vicinity of the glioblastoma cells. The protein influences
a small population of cancer cells, the so-called tumor
stem cells. The current consensus of researchers is that
these tumor stem cells are the actual cause for the
continuous tumor self-renewal in the brain. A small
quantity of these cells is sufficient to form new tumors
again even after surgery. BMP-7 induces signaling in the
tumor stem cells, causing them to differentiate. This
means that they are no longer tumor stem cells.
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However, the activity of stem cells in the brain and thus
of the body’s own protective mechanism against
glioblastomas diminishes with increasing age. This
could explain why the tumors usually develop in older
adults and not in children and young people.
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Aim – the destruction of tumor stem cells
The discovery of the tumor stem cells has led to new
concepts in the therapy of glioblastomas. “Normal
cancer cells” can be destroyed using conventional
therapies (surgery, radiation, chemotherapy), which
are seldom successful in tumor stem cells. The aim is
therefore to develop therapy concepts to destroy
these tumor stem cells. The findings from the mouse
experiments of the researchers in Berlin could point
to a new approach: reprogramming tumor stem cells
into less harmful cells, which could then be destroyed
with a therapy.
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