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

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posted on 2023-06-09, 15:02 authored by Thomas Simon, Sotiria Pinioti, Pascale Schellenberger, Vinothini Rajeeve, Franz Wendler, Pedro R Cutillas, Alice KingAlice King, Justin Stebbing, Georgios GiamasGeorgios Giamas
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.

Funding

Elucidating the role of MTK3 in Glioblastoma multiforme; G1867; ACTION AGAINST CANCER; 042016-07

History

Publication status

  • Published

File Version

  • Published version

Journal

Molecular Cancer

ISSN

1476-4598

Publisher

BMC (part of Springer Nature)

Issue

132

Volume

17

Page range

1-7

Department affiliated with

  • Biochemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-09-13

First Open Access (FOA) Date

2018-09-13

First Compliant Deposit (FCD) Date

2018-09-12

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