A class of extracellular vesicles from breast cancer cells activates VEGF receptors and tumour angiogenesis

Qiyu Feng, Chengliang Zhang, David Lum, Joseph E. Druso, Bryant Blank, Kristin F. Wilson, Alana Welm, Marc A. Antonyak and Richard A. Cerione ()
Additional contact information
Qiyu Feng: Cornell University
Chengliang Zhang: Cornell University
David Lum: Huntsman Cancer Institute, University of Utah
Joseph E. Druso: Cornell University
Bryant Blank: Cornell University
Kristin F. Wilson: Cornell University
Alana Welm: Huntsman Cancer Institute, University of Utah
Marc A. Antonyak: Cornell University
Richard A. Cerione: Cornell University

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: Abstract Non-classical secretory vesicles, collectively referred to as extracellular vesicles (EVs), have been implicated in different aspects of cancer cell survival and metastasis. Here, we describe how a specific class of EVs, called microvesicles (MVs), activates VEGF receptors and tumour angiogenesis through a unique 90 kDa form of VEGF (VEGF90K). We show that VEGF90K is generated by the crosslinking of VEGF165, catalysed by the enzyme tissue transglutaminase, and associates with MVs through its interaction with the chaperone Hsp90. We further demonstrate that MV-associated VEGF90K has a weakened affinity for Bevacizumab, causing Bevacizumab to be ineffective in blocking MV-dependent VEGF receptor activation. However, treatment with an Hsp90 inhibitor releases VEGF90K from MVs, restoring the sensitivity of VEGF90K to Bevacizumab. These findings reveal a novel mechanism by which cancer cell-derived MVs influence the tumour microenvironment and highlight the importance of recognizing their unique properties when considering drug treatment strategies.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms14450 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14450

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms14450

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().