Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cancer cells with a long breath: Seeking the origin of brain tumours in children

13.08.2008
Medulloblastoma is one of the most common and most malignant brain tumours among children and teenagers. These tumours grow very rapidly, and fifty percent of patients in the long term die from the condition.

The details of the processes that lead to the growth of these tumours have remained unknown until now. In two studies, working together with international scientific teams, LMU medical scientist Dr. Ulrich Schüller has now successfully revealed certain molecular mechanisms that lead to the development of these cerebellar tumours.

As reported in the current issue of the journal “Cancer Cell”, the researchers triggered genetic changes in cell populations in the brains of mice in order to provoke the growth of tumours. It turned out that medulloblastomas arose from only one type of cell – granule cells – and only if these were already fully committed. “Medulloblastomas are presently treated with nonspecific methods,” states Schüller. “Our results could contribute to the development of targeted therapies, and thus improve the treatment of cerebellar tumours in children.”

When children develop cancer, about every fifth tumour is a brain tumour – and every fifth of those in turn is a medulloblastoma. This common tumour occurs most of all in children under ten years of age, but also occurs in adults, albeit very infrequently. Up to now, medulloblastomas have only been treatable with the standard tools of cancer medicine: operation, radiotherapy and chemotherapy. Surgical interventions to treat this condition, like all operations on the brain, are particularly delicate, since it is difficult to remove the tumour completely without affecting healthy tissue. Because these cerebellar tumours scatter easily throughout the brain and even in the medullary canal, many cases result in metastases, that is the growth of secondary tumours, and not infrequently to a relapse of the original tumour – often even after successful conclusion of the treatment.

That is why patients and doctors are hoping for more targeted therapies that promise better therapeutic outcomes. “But for that to be possible, we first need to understand the principles of how the tumours develop,” says Schüller. “If we know how a tumour arises at the molecular level, we can also develop specific therapies that actually treat the cause of that particular condition.” Since it was still unknown from what type of cell and at what stage of development medulloblastomas arise, the researchers induced specific genetic changes in various cell populations in the brains of mice. This “conditional knock-out” method provoked changes in the so-called sonic hedgehog signalling pathway. Various processes in the development of nerve cells are controlled by this molecular signalling cascade. “Normally, the signalling pathway ensures a balance of growth and maturation of cells,” says Schüller. “But if disrupted, it can lead to uncontrolled growth of cells – and thus the onset of cancer”.

In another step, the research team investigated the effects of mutations on nerve cells in various stages of development. Multipotent progenitor cells have the ability – almost like stem cells – to develop into many different types of cell, while “unipotent” progenitor cells can only develop into one specific type of cell. “All of our studies have shown that medulloblastomas can only develop from granule cells and their progenitors,” Schüller tells us. “Other cells on the other hand, such as the large Purkinje cells of the cerebellum, do not become tumourigenic. They don’t seem bothered by these mutations at all.” And there is yet another distinctive result that the researchers achieved: the genetic changes only triggered one specific type of tumour: the medulloblastoma. Other brain tumours such as astrocytomas or oligodendrogliomas did not occur, even though, normally, the genetically attacked multipotent progenitors could have just as easily developed into astrocytes or oligodendrocytes.

It was especially surprising that even mutations in very early, immature cells triggered corresponding changes that only became tumourigenic if and when the cells had developed the characteristics of granule cells. The researchers were also surprised to find that the medulloblastomas appeared completely identical both morphologically and molecularly, no matter what stage of development they were triggered at. The researchers identified yet another factor in the development of medulloblastomas: the protein Olig2 has so far only been linked to the formation of glial cells in the brain, which primarily provide support for neurons. “But we also found Olig2 in progenitors of the granule cells of the cerebellum and in tumour cells,” reports neuropathologist Schüller. “That means this protein also influences the formation and multiplication of cancer cells – which makes it clear once again just how closely normal and malignant development processes resemble one another. We hope our results will contribute to a targeted therapy for medulloblastomas. That will require further research, however, which we already have in the planning.”

One of the funders of the studies was the German Cancer Aid, with whose assistance Schüller established one of two Max-Eder Young Investigator Groups at LMU.

Kathrin Bilgeri | alfa
Further information:
http://www.lmu.de

More articles from Health and Medicine:

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

nachricht Second cause of hidden hearing loss identified
20.02.2017 | Michigan Medicine - University of Michigan

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>