Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8
Berenguer, Jordi; Lagerweij, Tonny; Zhao, Xi Wen; Dusoswa, Sophie; van der Stoop, Petra; Westerman, Bart; Gooijer, Mark C.de; Zoetemelk, Marloes; Zomer, Anoek; Crommentuijn, Matheus H.W.; Wedekind, Laurine E.; López-López, Àlan; Giovanazzi, Alberta; Bruch-Oms, Marina; Meulen-Muileman, Ida H.van der; Reijmers, Rogier M.; van Kuppevelt, Toin H.; García-Vallejo, Juan Jesús; van Kooyk, Yvette; Tannous, Bakhos A.; Wesseling, Pieter; Koppers-Lalic, Danijela; Vandertop, W. Peter; Noske, David P.; van Beusechem, Victor W.; van Rheenen, Jacco; Pegtel, D. Michiel; Tellingen, Olaf van; Wurdinger, Thomas
(2018) Journal of Extracellular Vesicles, volume 7, issue 1, pp. 1 - 21
(Article)
Abstract
Cancer cells release extracellular vesicles (EVs) that contain functional biomolecules such as RNA and proteins. EVs are transferred to recipient cancer cells and can promote tumour progression and therapy resistance. Through RNAi screening, we identified a novel EV uptake mechanism involving a triple interaction between the chemokine receptor CCR8 on
... read more
the cells, glycans exposed on EVs and the soluble ligand CCL18. This ligand acts as bridging molecule, connecting EVs to cancer cells. We show that glioblastoma EVs promote cell proliferation and resistance to the alkylating agent temozolomide (TMZ). Using in vitro and in vivo stem-like glioblastoma models, we demonstrate that EV-induced phenotypes are neutralised by a small molecule CCR8 inhibitor, R243. Interference with chemokine receptors may offer therapeutic opportunities against EV-mediated cross-talk in glioblastoma.
show less
Download/Full Text
Keywords: CCR8, Chemokine receptor, Extracellular vesicles, glioblastoma, glycans, RNAi screening, temozolomide, therapy resistance, Histology, Cell Biology
ISSN: 2001-3078
Publisher: Taylor and Francis Ltd.
(Peer reviewed)
