The Luxembourg Centre of Neuropathology (LCNP) under the direction of Professor Michel Mittelbronn was established in collaboration with the Luxembourg Institute of Health (LIH), and the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg (UL). The LCNP research unit at the LIH targets different aspects of brain tumor biology.
Brain tumors describe the abnormal growth of tissue in the brain or the central spine that leads to a disruption of proper brain functions. Brain tumors can arise directly from cells within the brain (primary brain tumors) or derive from metastatic cells of peripheral tumors (metastatic or secondary brain tumors). The treatment of brain tumors is difficult due to the delicate localization within the central organ of the human nervous system. Accordingly, current research is strongly focused on improving treatment strategies to enhance affected patient survival.
Glioblastoma (GBM) is the most malignant primary brain tumor. Despite standard therapy, the median patient survival is around 14 months and the patients frequently relapse. This is due to tumor evolution, the clonal heterogeneity and the highly infiltrative character of a subset of tumor cells. It is a general notion that such subsets of pro-invasive tumor cells have distinct genetic signatures compared to cells of the tumor core. The “Identification and characterization of invasion-promoting genes in GBM” project aims to identify genes and downstream molecular players defining the infiltrative capacities of GBM tumor cells to reveal novel therapeutic targets for improved GBM treatment.
Tumorigenesis of brain tumors is not only driven by cell intrinsic mechanism but also strongly influenced by the tumor microenvironment. Amongst others microglial brain immune cells, are the most common cellular entities that interact with the GBM tumors representing up to 30–50% of the tumor mass. Tumor cells have been shown to interact with immune cells of the brain creating an immunosuppressive microenvironment. Our “Contribution of microglial reprogramming to glioblastoma progression : exploring DNA methylation” project addresses the question of epigenetic changes in microglia following interaction with GBM tumor cells. We assume that these epigenetic changes might cause the tumorigenesis promoting phenotype of brain microglia. We expect that further knowledge of the microglia-GBM crosstalk will be the basis for potential therapeutic strategies for improved treatment of brain tumors in general, and furthermore, pave the way to prevent the initiation of glioblastoma development in patients at risk to develop those tumors.
Metastatic brain tumors are associated with significant morbidity and mortality. Melanoma is one of the most frequent causes of secondary brain tumors. One critical stage leading to brain metastasis is the migration of cancer cells through the Blood-Brain-Barrier (BBB). Within the “Mechanism of brain metastasis in melanoma“ project, the LCNP research unit aims to decipher which processes metastasizing cells undergo when passing the BBB. Here, the unit intends to identify components that can be targeted in order to prevent the formation of brain metastases.
One of the major obstacles brain tumor treatment faces is the total surgical resection of all tumorigenic cells. The infiltrative capacity of several brain tumors prevents complete eradication of cancer cells and in contrast to many tumor entities in the periphery excessive brain tissue removal is impossible. The capability of precise differentiation between healthy versus tumor cell invaded brain tissue during surgery is therefore essential for the therapeutic success of brain tumor patients. “The use of Raman spectrometry in brain cancer diagnosis” project is a promising approach to improve intra-operative diagnostics. By collecting Raman spectra of brain tumor cohorts and further relate obtained data to neuropathological parameters this project aims to implement a classification of several brain tumor entities to optimize intra-operative optical diagnostic.
Current Research Projects
Mechanism of brain metastasis in melanoma
Exploring DNA methylation in GBM reprogrammed microglial cells
Identification and characterization of invasion-promoting genes in GBM
The use of Raman spectroscopy in brain cancer diagnostics
Head of Luxembourg Center of Neuropathology
Prof. Dr. Michel Mittelbronn is the head of Luxembourg Center of Neuropathology.