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 Cholesterol-lowering drugs may fight infectious disease
22.08.2017 | Duke University

nachricht Once invincible superbug squashed by 'superteam' of antibiotics
22.08.2017 | University at Buffalo

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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Researchers devise microreactor to study formation of methane hydrate

23.08.2017 | Materials Sciences

ShAPEing the future of magnesium car parts

23.08.2017 | Automotive Engineering

New insights into the world of trypanosomes

23.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>