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
Neutrons produce first direct 3D maps of water during cell membrane fusion
21.09.2018 | DOE/Oak Ridge National Laboratory
Narcolepsy, scientists unmask the culprit of an enigmatic disease
20.09.2018 | Universitätsspital Bern
The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.
This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.
Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...
Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.
"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...
A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.
Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...
Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.
An international team of researchers has mapped Nemo's genome, providing the research community with an invaluable resource to decode the response of fish to...
21.09.2018 | Event News
03.09.2018 | Event News
27.08.2018 | Event News
21.09.2018 | Physics and Astronomy
21.09.2018 | Life Sciences
21.09.2018 | Event News