Press release from Heidelberg University Hospital (UKHD)
Scientists from the University of Heidelberg, the Heidelberg University Hospital and the German Cancer Research Center have discovered how nerve cells in the brain establish contact with glioblastoma tumor cells and thus promote their spread. The team has now been honored by the Portuguese BIAL Foundation with the highly endowed "BIAL Award in Biomedicine". The scientists received the award from the Portuguese Minister of Health at a ceremony in Lisbon today.
The findings of the Heidelberg scientists shed new light on the interaction between brain tumors and nerve tissue: healthy nerve cells in the brain make contact with the tumor cells of glioblastomas and thus drive the growth of these incurable brain tumors. For these groundbreaking findings, published in the journal Nature in 2019, the team led by Dr. Dr. Varun Venkataramani, Professor Dr. Frank Winkler and Professor Dr. Thomas Kuner, who conduct research at the Heidelberg Medical Faculty of Heidelberg University, will receive the BIAL Award in Biomedicine on February 20, 2024. The prize, endowed with 300,000 euros, is awarded every two years by the Portuguese BIAL Foundation and recognizes a scientific discovery in the field of biomedicine of exceptional quality and scientific relevance.
The Heidelberg scientists will receive the award on behalf of all 29 authors of the article from the Portuguese Minister of Health, Manuel Pizarro, at a ceremony this evening. You can watch a recording of the event here.
Glioblastomas are highly aggressive brain tumors that are currently incurable. Despite intensive treatment with surgery, chemotherapy and radiotherapy, patients usually die within two years. In 2015, a team led by Professor Dr. Frank Winkler, head of the research group in the Neurooncology Clinical Cooperation Unit at the Heidelberg University Hospital (UKHD) and the German Cancer Research Center (DKFZ), discovered a reason for this: glioblastoma cells are connected to each other by long cell extensions and grow into the healthy brain like a fungal network. On the one hand, this network cannot be removed surgically; on the other hand, the cells exchange important substances via these connections and thus protect themselves from the damage caused by the therapy.
During his research in the laboratories of Prof. Winkler and Prof. Dr. Thomas Kuner, head of the Department of Functional Neuroanatomy at the Institute of Anatomy and Cell Biology, Dr. Dr. Varun Venkataramani discovered that the healthy nerve cells in the diseased brain act as collaborators of the hostile cells: using the electron microscope and other special microscopic techniques, he discovered that the nerve cells are in close contact with the tumor cells and form cell-cell contacts, so-called synapses. They use these synapses to transmit excitation signals to the long cell processes of the glioblastoma cells. This is a driving force for tumor growth and the proliferation of tumor cells into brain tissue. "We currently believe that brain activity supports the spread of glioblastoma," says Varun Venkataramani.
The researchers studied tumors of human glioblastoma cells transplanted into mice, cell cultures of human nerve and tumor cells, and tissue samples from patients. Among other things, they used a wide range of advanced microscopy techniques to visualize the micrometer-sized synapses and signal transmission to the tumor cells. "Only by using such a wide range of methods were we able to show that the cell-cell contacts on the nerve cell side are actually normal excitatory synapses that function in exactly the same way and can also be inhibited with the same active substances," says Professor Dr. Thomas Kuner. "This opened the door to clinical application.
For example, in animal studies, a drug used to treat epilepsy disrupted signaling from nerve cells to tumor cells. In mice given the drug, the glioblastoma grew much more slowly. "We didn't stop there, but worked quickly to get a clinical trial underway. Since January 2024, the first patients with recurrent glioblastoma have been receiving the epilepsy drug before surgery as part of this study," says Professor Winkler, who hopes that the results from 2019 will soon be able to support the treatment of those affected. Up to 66 patients from all over Germany will take part in the study, which is being conducted by the UKHD and the National Center for Tumor Diseases (NCT) in Heidelberg.
There is now growing scientific evidence that the nervous system may also play a central role in other types of cancer. For Venkataramani, Winkler and Kuner, the award-winning work is the cornerstone of a new field of research called "cancer neuroscience," which aims to explore the complex interactions between the nervous system and cancer. "Cancer neuroscience will play an increasingly important role in cancer research in the future. We will play our part, for example, in the collaborative research center "UNITE GLIOBLASTOMA - Overcoming Therapy Resistance of Glioblastomas (SFB1389)" and other planned research networks," says Winkler. The SFB UNITE GLIOBLASTOMA will be coordinated from Heidelberg. Its spokesperson is Professor Dr. Wolfgang Wick, Medical Faculty of the University of Heidelberg, Medical Director of the Neurological Clinic of the UKHD and Head of the Clinical Cooperation Unit "Neurooncology" of the UKHD and the DKFZ.
Image description
At the award ceremony in Lisbon (from left): Portuguese Health Minister Manuel Pizarro, Prof. Dr. Frank Winkler, Dr. Dr. Varun Venkataramani, Prof. Dr. Thomas Kuner and Luís Portela, Chairman of the BIAL Foundation. Source: BIAL Foundation
Literature
Venkataramani V, Tanev DI, Strahle C, et al. Glutamatergic synaptic input to glioma cells drives brain tumour progression. Nature. 2019;573(7775):532-538. doi:10.1038/s41586-019-1564-x
Videos
BIAL Award in Biomedicine 2023 - Award Ceremony - YouTube
Video zu den Preisträgern und ihrer Forschung
Further information
UKHD press release September 19, 2019: Nervenzellen feuern Hirntumorzellen zum Wachstum an
Neurology Clinic at the UKHD
Clinical Cooperation Unit Neurooncology
Institute of Anatomy and Cell Biology
Laboratory Dr. Dr. Venkataramani
Contact
Prof. Dr. med. Thomas Kuner
Director
Department of Functional Neuroanatomy
Institute of Anatomy and Cell Biology
Medical Faculty Heidelberg of the University of Heidelberg
E-mail: thomas.kuner@uni-heidelberg.de
Prof. Dr. med. Frank Winkler
Managing Senior Physician
Neurological University Hospital Heidelberg
Clinical Cooperation Unit Neurooncology, German Cancer Research Center
Medical Faculty Heidelberg of the University of Heidelberg
E-mail: frank.winkler@med.uni-heidelberg.de
Dr. med. Dr. rer. nat. Varun Venkataramani
Head of research group and resident in neurology
Neurological University Hospital Heidelberg
Department of Functional Neuroanatomy
Institute of Anatomy and Cell Biology
Clinical Cooperation Unit Neurooncology, German Cancer Research Center
Medical Faculty Heidelberg of the University of Heidelberg
E-mail: varun.venkataramani@med.uni-heidelberg.de
You can also find this press release online in our UKHD Newsroom.
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