Functional invadopodia formed in glioblastoma stem cells are important regulators of tumor angiogenesis

Oncotarget
Christos PetropoulosLucie Karayan-Tapon

Abstract

Glioblastoma (GBM) represents the most common and lethal brain tumor. High vascularization, necrosis and invasiveness are hallmarks of GBM aggressiveness with recent data suggesting the important role of glioblastoma stem cells (GSCs) in these processes. It is now well established that cancer cells employ specialized structures termed invadosomes to potentiate invasion. However, the role of these structures in GBM dissemination remains poorly investigated. In this study, we showed that GBM-isolated GSCs form invadopodia-like protrusions endowed with degradative action. Interestingly, their formation depends on extracellular matrix (ECM) sensing via the CD44 receptor. We also found that GSCs invasive migration occurring during tubes assembly is promoted through invadopodia-mediated-ECM remodeling and LIM kinases signaling. Moreover, our study demonstrates that GSCs are highly adaptable cells that are able not only to restore damaged endothelial-derived tubes but also to generate in cooperation with normal endothelial cells (ECs) intact vascular channels. Taken together, our data provide new insights in GBM microvasculature and suggest that GSCs targeting in combination with anti-VEGF therapy may block tumor progression.

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Citations

May 30, 2020·International Journal of Molecular Medicine·Kamariah IbrahimRahman Jamal
Sep 28, 2018·Neuromolecular Medicine·Marton TompaBernadette Kalman
Feb 10, 2019·International Journal of Molecular Sciences·Miguel QuintanillaEster Martín-Villar
Oct 3, 2020·Cells·Lucía Montero-MonteroEster Martín-Villar
May 1, 2021·International Journal of Molecular Sciences·Tomas KoltaiRosa A Cardone

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Datasets Mentioned

BETA
GM6001

Methods Mentioned

BETA
confocal microscopy
fluorescence imaging
transfection
Assay
electrophoresis

Software Mentioned

FV1000 Viewer
ImageJ
FluoView
NCSS
Imaris
Olympus
ToupView

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