Florence Lefranc1, Emilie Le Rhun2, Robert Kiss3, Michael Weller4. 1. Department of Neurosurgery, Hôpital Erasme; Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium. Electronic address: Florence.lefranc@erasme.ulb.ac.be. 2. University of Lille, U-1192, F-59000 Lille, France; Inserm, U-1192, F-59000 Lille, France; CHU Lille, General and Stereotaxic Neurosurgery Service, F-59000 Lille, France. 3. FRS-FNRS, Brussels, Belgium. 4. Department of Neurology, University Hospital & University of Zurich, Frauenklinikstrasse 26, CH-8091 Zurich, Switzerland.
Abstract
PURPOSE: The purpose of the current review is to highlight, on one hand, the fact that the migratory pattern of glioma cells is the major obstacle to combat them with chemotherapy, and on the other one, the new treatment strategies to overcome this obstacle. METHODS: This review surveys several membrane and extracellular molecules involved in glioma cell migration, invasiveness and resistance to apoptosis. RESULTS: This review focuses on signaling pathways implicated in the positive regulation of glioblastoma cell migration, including glutamate and ion channel networks, microtubes and membrane-derived extracellular vesicles (EV) containing microRNAs. Glioma cells release glutamate to the extracellular matrix, inducing neuronal cell death, which may facilitate glioma growth and invasion. Glioma cell migration and invasion are further facilitated through ion channels and transporters that modify cellular volume. Microtubes and EV promote connections and communication among glioma cells and with the microenvironment and are associated with progression and resistance to therapy. Potential therapies linked to these pathways for glioblastoma are being developed. CONCLUSION: Our view is evolving from an intracellular view of the complex intracellular signaling pathways to one of orchestral machinery, including connections between heterogeneous tumoral and nontumoral cells and with the microenvironment through channels, microtubes, and extracellular miRNA, generating different signals at different times. All of these elements give rise to a new perspective for the treatment of glioblastoma.
PURPOSE: The purpose of the current review is to highlight, on one hand, the fact that the migratory pattern of glioma cells is the major obstacle to combat them with chemotherapy, and on the other one, the new treatment strategies to overcome this obstacle. METHODS: This review surveys several membrane and extracellular molecules involved in glioma cell migration, invasiveness and resistance to apoptosis. RESULTS: This review focuses on signaling pathways implicated in the positive regulation of glioblastoma cell migration, including glutamate and ion channel networks, microtubes and membrane-derived extracellular vesicles (EV) containing microRNAs. Glioma cells release glutamate to the extracellular matrix, inducing neuronal cell death, which may facilitate glioma growth and invasion. Glioma cell migration and invasion are further facilitated through ion channels and transporters that modify cellular volume. Microtubes and EV promote connections and communication among glioma cells and with the microenvironment and are associated with progression and resistance to therapy. Potential therapies linked to these pathways for glioblastoma are being developed. CONCLUSION: Our view is evolving from an intracellular view of the complex intracellular signaling pathways to one of orchestral machinery, including connections between heterogeneous tumoral and nontumoral cells and with the microenvironment through channels, microtubes, and extracellular miRNA, generating different signals at different times. All of these elements give rise to a new perspective for the treatment of glioblastoma.
Authors: Dorothee Gramatzki; James Louis Rogers; Marian Christoph Neidert; Caroline Hertler; Emilie Le Rhun; Patrick Roth; Michael Weller Journal: Neurooncol Pract Date: 2020-04-25
Authors: Pinar Uysal-Onganer; Amy MacLatchy; Rayan Mahmoud; Igor Kraev; Paul R Thompson; Jameel M Inal; Sigrun Lange Journal: Int J Mol Sci Date: 2020-02-22 Impact factor: 5.923