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; 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

doi:10.1080/20013078.2018.1446660

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. TannousPieter 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

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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 language	English
Article number	1446660
Journal	Journal of Extracellular Vesicles
Volume	7
Issue number	1
DOIs	https://doi.org/10.1080/20013078.2018.1446660
Publication status	Published - 1 Jan 2018

Keywords

CCR8
Chemokine receptor
Extracellular vesicles
glioblastoma
glycans
RNAi screening
temozolomide
therapy resistance

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10.1080/20013078.2018.1446660

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Berenguer, J., Lagerweij, T., Zhao, X. W., Dusoswa, S., van der Stoop, P., Westerman, B., Gooijer, M. C. D., Zoetemelk, M., Zomer, A., Crommentuijn, M. H. W., Wedekind, L. E., López-López, À., Giovanazzi, A., Bruch-Oms, M., Meulen-Muileman, I. H. V. D., Reijmers, R. M., van Kuppevelt, T. H., García-Vallejo, J. J., van Kooyk, Y., ... Wurdinger, T. (2018). Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8. Journal of Extracellular Vesicles, 7(1), Article 1446660. https://doi.org/10.1080/20013078.2018.1446660

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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 Gooijer, {Mark C.de} 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 Tellingen, {Olaf van} and Thomas Wurdinger",

note = "Publisher Copyright: {\textcopyright} 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles.",

year = "2018",

month = jan,

day = "1",

doi = "10.1080/20013078.2018.1446660",

language = "English",

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journal = "Journal of Extracellular Vesicles",

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Berenguer, J, Lagerweij, T, Zhao, XW, Dusoswa, S, van der Stoop, P, Westerman, B, Gooijer, MCD, Zoetemelk, M, Zomer, A, Crommentuijn, MHW, Wedekind, LE, López-López, À, Giovanazzi, A, Bruch-Oms, M, Meulen-Muileman, IHVD, Reijmers, RM, van Kuppevelt, TH, García-Vallejo, JJ, van Kooyk, Y, Tannous, BA, Wesseling, P, Koppers-Lalic, D, Vandertop, WP, Noske, DP, van Beusechem, VW, van Rheenen, J, Pegtel, DM, Tellingen, OV & Wurdinger, T 2018, 'Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8', Journal of Extracellular Vesicles, vol. 7, no. 1, 1446660. https://doi.org/10.1080/20013078.2018.1446660

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 - Gooijer, Mark C.de

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 - Tellingen, Olaf van

AU - Wurdinger, Thomas

PY - 2018/1/1

Y1 - 2018/1/1

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

AN - SCOPUS:85044069544

SN - 2001-3078

VL - 7

JO - Journal of Extracellular Vesicles

JF - Journal of Extracellular Vesicles

IS - 1

M1 - 1446660

ER -

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

Abstract

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