[Letter to editor] Shedding of bevacizumab in tumour cells derived extracellular vesicles as a new therapeutic escape mechanism in glioblastoma

Simon, Thomas, Pinioti, Sotiria, Schellenberger, Pascale, Rajeeve, Vinothini, Wendler, Franz, Cutillas, Pedro R, King, Alice, Stebbing, Justin and Giamas, Georgios (2018) [Letter to editor] Shedding of bevacizumab in tumour cells derived extracellular vesicles as a new therapeutic escape mechanism in glioblastoma. Molecular Cancer, 17 (132). pp. 1-7. ISSN 1476-4598

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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 cells improved the anti-tumour effect of bevacizumab. Together, this data suggests of a potential new mechanism of GBM escape from bevacizumab activity.

Item Type: Article
Keywords: Bevacizumab, Extracellular vesicles, Glioblastoma, Resistance
Schools and Departments: School of Life Sciences > Biochemistry
School of Mathematical and Physical Sciences > Physics and Astronomy
Subjects: Q Science
Q Science > Q Science (General) > Q0179.9 Research
Q Science > Q Science (General)
Related URLs:
Depositing User: Georgios Giamas
Date Deposited: 13 Sep 2018 08:36
Last Modified: 18 Feb 2022 13:33
URI: http://sro.sussex.ac.uk/id/eprint/78685

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Project NameSussex Project NumberFunderFunder Ref
Elucidating the role of MTK3 in Glioblastoma multiformeG1867ACTION AGAINST CANCER042016-07