Extracellular vesicles as central regulators of blood vessel function in cancer

Kugeratski, F. G., Santi, A. and Zanivan, S. (2022) Extracellular vesicles as central regulators of blood vessel function in cancer. Science Signaling, 15(753), eaaz4742. (doi: 10.1126/scisignal.aaz4742) (PMID:36166511)

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Blood vessels deliver oxygen and nutrients that sustain tumor growth and enable the dissemination of cancer cells to distant sites and the recruitment of intratumoral immune cells. In addition, the structural and functional abnormalities of the tumor vasculature foster the development of an aggressive tumor microenvironment and impair the efficacy of existing cancer therapies. Extracellular vesicles (EVs) have emerged as major players of tumor progression, and a growing body of evidence has demonstrated that EVs derived from cancer cells trigger multiple responses in endothelial cells that alter blood vessel function in tumors. EV-mediated signaling in endothelial cells can occur through the transfer of functional cargos such as miRNAs, lncRNAs, cirRNAs, and proteins. Moreover, membrane-bound proteins in EVs can elicit receptor-mediated signaling in endothelial cells. Together, these mechanisms reprogram endothelial cells and contribute to the sustained exacerbated angiogenic signaling typical of tumors, which, in turn, influences cancer progression. Targeting these angiogenesis-promoting EV-dependent mechanisms may offer additional strategies to normalize tumor vasculature. Here, we discuss the current knowledge pertaining to the contribution of cancer cell–derived EVs in mechanisms regulating blood vessel functions in tumors. Moreover, we discuss the translational opportunities in targeting the dysfunctional tumor vasculature using EVs and highlight the open questions in the field of EV biology that can be addressed using mass spectrometry–based proteomics analysis.

Item Type:Articles
Additional Information:This work was funded by Cancer Research UK [CRUK Beatson Institute A17196, CRUK Glasgow Centre A18076, Stand Up to Cancer campaign for Cancer Research UK A29800 (to S.Z.), and Breast Cancer Now 2018NovPR102 (to S.Z.)].
Glasgow Author(s) Enlighten ID:Zanivan, Professor Sara and Kugeratski, Fernanda Grande
Authors: Kugeratski, F. G., Santi, A., and Zanivan, S.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Science Signaling
Publisher:American Association for the Advancement of Science
ISSN (Online):1937-9145

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190874CR-UK Centre renewalKaren VousdenCancer Research UK (CRUK)C596/A18076Institute of Cancer Sciences