TY - JOUR
T1 - Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8
AU - Berenguer, Jordi
AU - Lagerweij, Tonny
AU - Zhao, Xi Wen
AU - Dusoswa, Sophie
AU - van der Stoop, Petra
AU - Westerman, Bart
AU - de Gooijer, Mark C.
AU - Zoetemelk, Marloes
AU - Zomer, Anoek
AU - Crommentuijn, Matheus H.W.
AU - Wedekind, Laurine E.
AU - López-López, Àlan
AU - Giovanazzi, Alberta
AU - Bruch-Oms, Marina
AU - Meulen-Muileman, Ida H.van der
AU - Reijmers, Rogier M.
AU - van Kuppevelt, Toin H.
AU - García-Vallejo, Juan Jesús
AU - van Kooyk, Yvette
AU - Tannous, Bakhos A.
AU - Wesseling, Pieter
AU - Koppers-Lalic, Danijela
AU - Vandertop, W. Peter
AU - Noske, David P.
AU - van Beusechem, Victor W.
AU - van Rheenen, Jacco
AU - Pegtel, D. Michiel
AU - van Tellingen, Olaf
AU - Wurdinger, Thomas
PY - 2018/3/13
Y1 - 2018/3/13
N2 - 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 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.
AB - 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 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.
KW - CCR8
KW - Chemokine receptor
KW - Extracellular vesicles
KW - RNAi screening
KW - glioblastoma
KW - glycans
KW - temozolomide
KW - therapy resistance
UR - http://www.scopus.com/inward/record.url?scp=85044069544&partnerID=8YFLogxK
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85044069544&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29696074
U2 - https://doi.org/10.1080/20013078.2018.1446660
DO - https://doi.org/10.1080/20013078.2018.1446660
M3 - Article
C2 - 29696074
SN - 2001-3078
VL - 7
JO - Journal of extracellular vesicles
JF - Journal of extracellular vesicles
IS - 1
M1 - 1446660
ER -