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Vascular permeability in the RG2 glioma model can be mediated by macropinocytosis and be independent of the opening of the tight junction

Karin Pernet-Gallay 1 Pierre-Henri Jouneau 2 Anne Bertrand 3 Julie Delaroche 1 Régine Farion 1 Chantal Remy 1 Emmanuel L. Barbier 4 
2 Physiopathologie du Cytosquelette
GIN - [GIN] Grenoble Institut des Neurosciences
3 ARAMIS - Algorithms, models and methods for images and signals of the human brain
UPMC - Université Pierre et Marie Curie - Paris 6, ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute, Inria de Paris
Abstract : This study evaluates the extravasation pathways of circulating macromolecules in a rat glioma model (RG2) which was observed by both magnetic resonance imaging using ultrasmall superparamagnetic iron oxide and electron microscopy. Although magnetic resonance imaging signal enhancement was observed as soon as 10min after injection (9.4% 2h after injection), electron microscopy showed that endothelial cells were still tightly sealed. However, circulating immunoglobulin G and ultrasmall superparamagnetic iron oxide were found in large membrane compartments of endothelial cells, in the basal lamina (7.4 +/- 1.2 gold particles/mu m(2) in the tumor versus 0.38 +/- 0.17 in healthy tissue, p=1.4.10(-5)) and between tumoral cells. Altogether, this strongly suggests an active transport mediated by macropinocytosis. To challenge this transport mechanism, additional rats were treated with amiloride, an inhibitor of macropinocytosis, leading to a reduction of membrane protrusions (66%) and of macropinosomes. Amiloride however also opened tumoral tight junctions allowing a larger extravasation of ultrasmall superparamagnetic iron oxide (magnetic resonance imaging signal enhancement of 35.7% 2h after injection). Altogether, these results suggest that ultrasmall superparamagnetic iron oxide and immunoglobulin G in the RG2 glioma model follow an active extravasation pathway mediated by a macropinocytosis process. Amiloride also appears as a potential strategy to facilitate the extravasation of chemotherapeutic drugs in glioma.
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Submitted on : Friday, October 7, 2016 - 6:39:58 PM
Last modification on : Thursday, August 4, 2022 - 5:21:29 PM

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Karin Pernet-Gallay, Pierre-Henri Jouneau, Anne Bertrand, Julie Delaroche, Régine Farion, et al.. Vascular permeability in the RG2 glioma model can be mediated by macropinocytosis and be independent of the opening of the tight junction. Journal of Cerebral Blood Flow and Metabolism, 2017, 37 (4), pp.1264-1275. ⟨10.1177/0271678X16654157⟩. ⟨hal-01377878⟩



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