Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Pediatric brain tumors

21.09.2011
Regulatory protein represents potential drug target

Medulloblastomas constitute the most frequent class of malignant childhood brain tumor. Tumors of this type arise due to the uncontrolled proliferation of immature nerve cells in the developing brain, and there is no targeted treatment available.

A research team based at LMU‘s Center for Neuropathology and Prion Research and led by Privatdozent Dr. Ulrich Schüller has now demonstrated that the regulatory protein FoxM1 is essential for the continued growth of these tumor cells. Moreover, the level of FoxM1 expressed in the cells is significantly, and negatively, correlated with a patient’s survival time.

The protein therefore provides a useful prognostic marker, which should allow oncologists to gauge the malignancy of tumors and select the most effective therapeutic strategy for the individual patient. Furthermore, FoxM1 may provide a novel point of attack for the development of new ways to treat the condition. Schüller and his team were able to reduce FoxM1 levels in tumor cells by exposing them to the antibiotic siomycin A, and showed that the drug also inhibits tumor growth. “If further work on laboratory cell cultures and in living organisms confirms these results, siomycin could turn out to be an effective drug for the treatment of medulloblastoma,” Schüller says. (Clinical Cancer Research, published OnlineFirst 14.September 2011)

Research conducted over the past 10 years has shown that medulloblastomas arise as a result of aberrant activation of certain molecular signaling pathways. Schüller and his team set out to determine whether the transcription factor FoxM1 plays a role in supporting the growth of this type of tumor and, if so, whether it might serve as a drug target for the development of an effective therapy for the disease.

Transcription factors determine the suite of proteins present in a given cell by defining which of the genes encoded in the genomic DNA are transcribed into RNA copies that can program protein synthesis. The so-called Forkhead-box (Fox) proteins are transcription factors that are particularly concerned with the regulation of cell growth, division and differentiation, and fully differentiated cells do not proliferate further. FoxM1 activates genes that promote cell division and simultaneously turns off genes that inhibit proliferation. Since uncontrolled proliferation is the basic hallmark of cancer cells, understanding and manipulating the function of FoxM1 has become a focus of cancer research. In several different types of cancer, including cancers of the breast, lung and prostate gland, increased amounts of FoxM1 have been found in tumor tissue. Indeed the protein has been shown to be necessary for growth of these tumors. Schüller and his team have now shown that this also true for medulloblastomas.

“One important result was that the amount of FoxM1 present in medulloblastoma cells is correlated with patient survival time,” says Schüller. Since it is relatively easy to estimate FoxM1 levels using laboratory tests, the molecule could possibly be used as a prognostic marker to guide the choice of treatment for each patient. Modern therapeutic options for medulloblastoma involve surgical removal of the tumor, followed by radiation and chemotherapy to eliminate any surviving tumor cells, but this approach is associated with serious side-effects. Furthermore, there are six different subtypes of medulloblastoma, which differ markedly in their malignancy and clinical prognosis. “That is why a good prognostic marker with which one could predict the aggressivity of tumors would be so useful,” says Schüller. The clinician could then adapt the therapeutic approach to the patient’s individual needs, and thus avoid using a sledgehammer to crack a nut.

Since FoxM1 is indispensable for the growth of medulloblastoma cells, it represents a potentially ideal drug target. With the aid of the antibiotic siomycin A, which specifically inhibits the production of FoxM1, Schüller was indeed able to inhibit the growth of medulloblastoma cells. These findings confirm and extend results obtained by other groups who have reported that siomycin A also hinders the growth of breast cancer cells. – And most importantly, Schüller‘s experiments showed that although FoxM1 is essential for tumor growth, other factors can apparently substitute for it during normal development. Hence blocking the action of FoxM1 by administering siomycin A should have no untoward effects on normal cells. Thus the antibiotic may make it possible, for the first time, to intervene directly and specifically in the process that gives rise to medulloblastomas, and provide the first therapeutic option that targets a major driver of the growth of such tumors.

The work was carried out by the Max Eder Junior Research Group in Pediatric Neuro-oncology, which is led by Ulrich Schüller and is supported by grants from the Deutsche Krebshilfe. (göd/PH)

Publication:
Expression of FoxM1 is required for the proliferation of medulloblastoma cells and indicates worse survival of patients.
M. Priller, J. Pöschl, L. Abrao, A.O. von Bueren, Y.-J. Cho, S. Rutkowski, H.A. Kretzschmar, U. Schüller
Clinical Cancer Research, Published OnlineFirst 14. September 2011
doi: 10.1158/1078-0432.CCR-11-1214
Contact:
Priv.-Doz. Dr. med. Ulrich Schüller
Center for Neuropathology
LMU Munich
Phone: +49 89 2180 78114
Fax: +49 89 2180 78037
Email: ulrich.schueller@med.uni-muenchen.de

Dr. Kathrin Bilgeri | EurekAlert!
Further information:
http://www.neuropathologie.med.uni-muenchen.de

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>