Shedding of bevacizumab in tumour cells-derived extracellular vesicles as a new therapeutic escape mechanism in glioblastoma

Molecular Cancer
Thomas SimonGeorgios Giamas

Abstract

Glioblastoma (GBM) is the most aggressive type of primary brain tumours. Anti-angiogenic therapies (AAT), such as bevacizumab, have been developed to target the tumour blood supply. However, GBM presents mechanisms of escape from AAT activity, including a speculated direct effect of AAT on GBM cells. Furthermore, bevacizumab can alter the intercellular communication of GBM cells with their direct microenvironment. Extracellular vesicles (EVs) have been recently described as main acts in the GBM microenvironment, allowing tumour and stromal cells to exchange genetic and proteomic material. Herein, we examined and described the alterations in the EVs produced by GBM cells following bevacizumab treatment. Interestingly, bevacizumab that is able to neutralise GBM cells-derived VEGF-A, was found to be directly captured by GBM cells and eventually sorted at the surface of the respective EVs. We also identified early endosomes as potential pathways involved in the bevacizumab internalisation by GBM cells. Via MS analysis, we observed that treatment with bevacizumab induces changes in the EVs proteomic content, which are associated with tumour progression and therapeutic resistance. Accordingly, inhibition of EVs production by GBM cell...Continue Reading

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Citations

Apr 13, 2019·Annual Review of Genomics and Human Genetics·Michael W Graner
Jul 6, 2019·Frontiers in Oncology·Francesco MannavolaFrancesco Silvestris
May 1, 2020·International Journal of Molecular Sciences·Thomas SimonGeorgios Giamas
Sep 11, 2020·International Journal of Molecular Sciences·Gaetano PezzicoliFrancesco Mannavola
Feb 11, 2020·Frontiers in Immunology·Anuroop YekulaLeonora Balaj
Aug 11, 2020·Frontiers in Cell and Developmental Biology·Christopher Montemagno, Gilles Pagès
Oct 30, 2019·Journal of Neuroinflammation·Aurélie SoubéranGeneviève Rougon
Dec 5, 2019·International Journal of Molecular Sciences·Mercedes HerreraCristina Peña
Dec 24, 2019·Critical Reviews in Clinical Laboratory Sciences·Clarissa A WhiteheadStanley S Stylli
Aug 18, 2020·Oncogene·Quentin SabbaghJulie Gavard
Aug 23, 2020·International Journal of Molecular Sciences·Wioletta OlejarzTomasz Lorenc
Oct 22, 2020·International Journal of Molecular Sciences·Ancuta JurjIoana Berindan-Neagoe
Oct 24, 2020·Nanomedicine·Juliete Nathali SchollFabrício Figueiró
Nov 13, 2020·Frontiers in Cell and Developmental Biology·Tahereh GharbiGuo-Yuan Yang
Dec 20, 2020·Pharmaceuticals·Yusuke FunakoshiMasahiro Mizoguchi
Feb 16, 2021·Journal of Cellular and Molecular Medicine·Shuqiong ZhangLisong Shen
Dec 29, 2020·Frontiers in Cell and Developmental Biology·Ye Zeng, Bingmei M Fu
Mar 7, 2021·Cancers·Hong-My NguyenDipongkor Saha
Jul 3, 2021·International Journal of Molecular Sciences·Sara Rosińska, Julie Gavard
Jan 20, 2021·ACS Biomaterials Science & Engineering·Costanza MartelliGeorgios Giamas

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Methods Mentioned

BETA
immunoprecipitation
co-immunoprecipitation
Assay

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