Dra. Pilar Sánchez-Gómez, Principal Investigator- Neurooncology Unit- Instituto de Salud Carlos III- Madrid
"Tumor genotype defines the vascular phenotype: the paradigmatic case of gliomas"
Cancer growth is driven by the complex interplay between tumor cells and their supportive microenvironment. However, this interaction is still not fully understood, especially for gliomas, which are very aggressive brain tumors. Recent results from our group indicate that the genomic background of gliomas controls tumor progression by modifying the vascular microenvironment. Thus, we have described that the expression of TAU, a microtubule binding protein that has been classically associated with neurodegenerative diseases, is epigenetically induced by the presence of mutations in IDH1/2, typical of lower grade gliomas. Moreover, we found that TAU expression is inversely correlated with overall survival in EGFR-amplified gliomas. Using orthotopic EGFR-related models, we have observed that TAU overexpression or microtubule stabilizers impair the mesenchymal transformation of glioma cells, normalizing the vasculature and decreasing tumor burden. However, epithelial-to-mesenchymal transformed EGFR-mutant cells, acting as pericytes, induce neo-vasculogenesis, reduce vascular leakage and favor aggressive glioma growth, a process that is no longer sensitive to TAU. Altogether, our results indicate that the main genetic alterations of gliomas dictate the plasticity of tumor cells and shape the vascular landscape, which controls tumor progression. These data have important implications for the clinical management of glioma patients, from tumor classification to treatment.
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