Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8

Jordi Berenguer, Tonny Lagerweij, Xi Wen Zhao, Sophie Dusoswa, Petra van der Stoop, Bart Westerman, Mark C. de Gooijer, Marloes Zoetemelk, Anoek Zomer, Matheus H.W. Crommentuijn, Laurine E. Wedekind, Àlan López-López, Alberta Giovanazzi, Marina Bruch-Oms, Ida H.van der Meulen-Muileman, Rogier M. Reijmers, Toin H. van Kuppevelt, Juan Jesús García-Vallejo, Yvette van Kooyk, Bakhos A. Tannous & 9 others Pieter Wesseling, Danijela Koppers-Lalic, W. Peter Vandertop, David P. Noske, Victor W. van Beusechem, Jacco van Rheenen, D. Michiel Pegtel, Olaf van Tellingen, Thomas Wurdinger

Research output: Contribution to journalArticleAcademicpeer-review

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 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.

Original languageEnglish
Article number1446660
JournalJournal of Extracellular Vesicles
Volume7
Issue number1
DOIs
Publication statusPublished - 13 Mar 2018

Cite this

Berenguer, Jordi ; Lagerweij, Tonny ; Zhao, Xi Wen ; Dusoswa, Sophie ; van der Stoop, Petra ; Westerman, Bart ; de Gooijer, Mark C. ; 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 ; van Tellingen, Olaf ; Wurdinger, Thomas. / Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8. In: Journal of Extracellular Vesicles. 2018 ; Vol. 7, No. 1.
@article{6ea57db2161d4eaa828fe8b73bd87a01,
title = "Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8",
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 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.",
keywords = "CCR8, Chemokine receptor, Extracellular vesicles, glioblastoma, glycans, RNAi screening, temozolomide, therapy resistance",
author = "Jordi Berenguer and Tonny Lagerweij and Zhao, {Xi Wen} and Sophie Dusoswa and {van der Stoop}, Petra and Bart Westerman and {de Gooijer}, {Mark C.} and Marloes Zoetemelk and Anoek Zomer and Crommentuijn, {Matheus H.W.} and Wedekind, {Laurine E.} and {\`A}lan L{\'o}pez-L{\'o}pez and Alberta Giovanazzi and Marina Bruch-Oms and Meulen-Muileman, {Ida H.van der} and Reijmers, {Rogier M.} and {van Kuppevelt}, {Toin H.} and Garc{\'i}a-Vallejo, {Juan Jes{\'u}s} and {van Kooyk}, Yvette and Tannous, {Bakhos A.} and Pieter Wesseling and Danijela Koppers-Lalic and Vandertop, {W. Peter} and Noske, {David P.} and {van Beusechem}, {Victor W.} and {van Rheenen}, Jacco and Pegtel, {D. Michiel} and {van Tellingen}, Olaf and Thomas Wurdinger",
year = "2018",
month = "3",
day = "13",
doi = "10.1080/20013078.2018.1446660",
language = "English",
volume = "7",
journal = "Journal of Extracellular Vesicles",
issn = "2001-3078",
publisher = "Taylor and Francis Ltd.",
number = "1",

}

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; de Gooijer, Mark C.; 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; van Tellingen, Olaf; Wurdinger, Thomas.

In: Journal of Extracellular Vesicles, Vol. 7, No. 1, 1446660, 13.03.2018.

Research output: Contribution to journalArticleAcademicpeer-review

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 - glioblastoma

KW - glycans

KW - RNAi screening

KW - temozolomide

KW - therapy resistance

UR - http://www.scopus.com/inward/record.url?scp=85044069544&partnerID=8YFLogxK

U2 - 10.1080/20013078.2018.1446660

DO - 10.1080/20013078.2018.1446660

M3 - Article

VL - 7

JO - Journal of Extracellular Vesicles

JF - Journal of Extracellular Vesicles

SN - 2001-3078

IS - 1

M1 - 1446660

ER -