Cell-to-cell communication mediates glioblastoma progression in drosophila
journal contributionposted on 18.01.2021, 02:14 by Marta Portela-Esteban, T Mitchell, S Casas-Tintó
© 2020. Published by The Company of Biologists Ltd. Glioblastoma (GB) is the most aggressive and lethal tumour of the central nervous system (CNS). GB cells grow rapidly and display a network of projections, ultra-long tumour microtubes (TMs), that mediate cell to cell communication. GB-TMs infiltrate throughout the brain, enwrap neurons and facilitate the depletion of the signalling molecule wingless (Wg)/WNT from the neighbouring healthy neurons. GB cells establish a positive feedback loop including Wg signalling upregulation that activates cJun N-terminal kinase (JNK) pathway and matrix metalloproteases (MMPs) production, which in turn promote further TMs infiltration, GB progression and neurodegeneration. Thus, cellular and molecular signals other than primary mutations emerge as central players of GB. Using a Drosophila model of GB, we describe the temporal organisation of the main cellular events that occur in GB, including cell-to-cell interactions, neurodegeneration and TM expansion. We define the progressive activation of JNK pathway signalling in GB mediated by the receptor Grindelwald (Grnd) and activated by the ligand Eiger (Egr)/TNFα produced by surrounding healthy brain tissue. We propose that cellular interactions of GB with the healthy brain tissue precede TM expansion and conclude that non-autonomous signals facilitate GB progression. These results contribute to deciphering the complexity and versatility of these incurable tumours.
We acknowledge the support of the Confocal Microscopy unit and Molecular Biology unit at the Cajal Institute for their help with this project. Research was funded by grant BFU2015-65685P from the Spanish Ministry of Science and Innovation (MICINN).
Article NumberARTN bio053405
PublisherCOMPANY BIOLOGISTS LTD
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Science & TechnologyLife Sciences & BiomedicineBiologyLife Sciences & Biomedicine - Other TopicsGliaCancerGlioblastomaTumour microtubesJNKNeurodegenerationWORLD-HEALTH-ORGANIZATIONJNK-DEPENDENT APOPTOSISCENTRAL-NERVOUS-SYSTEMMATRIX METALLOPROTEINASESMALIGNANT GLIOMAEPITHELIAL-CELLSMODEL SYSTEMEXPRESSIONMMP-9RECEPTOR