Dysregulated Migration and Differentiation – A Molecular and Cellular Dissection of Cancer Stem Cells in High-Grade Gliomas

Coordinator:    PD Dr. Peter Hau
Institution: Klinik und Poliklinik für Neurologie, Universität Regensburg
This subproject aims at the understanding of genetic, molecular and cellular mechanisms of the pathogenesis of glioblastomas (GBMs) by identifying molecules and pathways that control GBM cell migration and differentiation.
Based on the Cancer Stem Cell (CSC) theory, which postulates that stem cells derived from Neural Stem Cells (NSC) are at the origin of gliomas, transformed NSCs escape from the tight control of the spatially and temporally orchestrated sequence of differentiation, migration and proliferation. In most cases, migration of NSCs is the first apparent step towards differentiation, and therefore, the analysis of differentiation and migration is closely connected. Vice versa, deregulated differentiation or migration may lead to the release of the proliferation control and to tumor formation through CSCs. Hence, the specific aims of the project are to identify differences in the pattern of differentiation in respect of migration of CSCs and normal NSCs, to investigate whether defunctional migration of CSCs is a central event in the pathogenesis of GBMs, and to identify and reverse the molecular mechanisms leading to misguided migration of CSCs and subsequent dedifferentiation. An understanding of these mechanisms may enable the therapeutic differentiation of CSCs into Tumor Cells (TCs), thereby blocking the pathway into an constantly renewing tumor. Secondly, by inhibiting the migration of CSCs, GBMs potentially might become a localized disease
amenable to curative treatment.
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