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
Diverse amyloid structures and dynamics revealed by high-speed atomic force microscopy
04.08.2020 | Kanazawa University
New approach for targeted cancer immunotherapy
30.07.2020 | Universität Basel
Traditional single-cell sequencing methods help to reveal insights about cellular differences and functions - but they do this with static snapshots only...
“Core-shell” clusters pave the way for new efficient nanomaterials that make catalysts, magnetic and laser sensors or measuring devices for detecting electromagnetic radiation more efficient.
Whether in innovative high-tech materials, more powerful computer chips, pharmaceuticals or in the field of renewable energies, nanoparticles – smallest...
An international research team with Prof. Cornelia Denz from the Institute of Applied Physics at the University of Münster develop for the first time light fields using caustics that do not change during propagation. With the new method, the physicists cleverly exploit light structures that can be seen in rainbows or when light is transmitted through drinking glasses.
Modern applications as high resolution microsopy or micro- or nanoscale material processing require customized laser beams that do not change during...
Although no life has been detected on the Martian surface, a new study from astrophysicist and research scientist at the Center for Space Science at NYU Abu...
New approach creates synthetic layered magnets with unprecedented level of control over their magnetic properties
The magnetic properties of a chromium halide can be tuned by manipulating the non-magnetic atoms in the material, a team, led by Boston College researchers,...
23.07.2020 | Event News
21.07.2020 | Event News
07.07.2020 | Event News
04.08.2020 | Life Sciences
04.08.2020 | Medical Engineering
04.08.2020 | Ecology, The Environment and Conservation