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

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 (VEGF_90K). We show that VEGF_90K 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 VEGF_90K has a weakened affinity for Bevacizumab, causing Bevacizumab to be ineffective in blocking MV-dependent VEGF receptor activation. However, treatment with an Hsp90 inhibito

SUBMITTER: Feng Q 

PROVIDER: S-EPMC5316898 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature