PT  - JOURNAL ARTICLE
AU  - Nicholas Ariotti
AU  - Yeping Wu
AU  - Satomi Okano
AU  - Yann Gambin
AU  - Jordan Follett
AU  - James Rae
AU  - Charles Ferguson
AU  - Rohan D. Teasdale
AU  - Kirill Alexandrov
AU  - Frederic A. Meunier
AU  - Michelle M. Hill
AU  - Robert G. Parton
TI  - An inverted Caveolin-1 topology defines a novel exosome secreted from prostate cancer cells
AID  - 10.1101/2020.03.19.999441
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.19.999441
4099  - http://biorxiv.org/content/early/2020/03/20/2020.03.19.999441.short
4100  - http://biorxiv.org/content/early/2020/03/20/2020.03.19.999441.full
AB  - Caveolin-1 (Cav1) expression and secretion is associated with prostate cancer (PCa) disease progression but the mechanisms underpinning Cav1 release remain poorly understood. Numerous studies have shown Cav1 can be secreted within exosome-like vesicles, but antibody-mediated neutralization can mitigate PCa progression; this is suggestive of an inverted (non-exosomal) Cav1 topology. Here we show that Cav1 can be secreted from specific PCa types in an inverted vesicle-associated form consistent with the features of bioactive Cav1 secretion. Characterization of the isolated vesicles by electron microscopy, single molecule fluorescent microscopy and proteomics reveals they represent a novel class of exosomes ∼40 nm in diameter containing ∼50-60 copies of Cav1 and strikingly, are released via a non-canonical secretory autophagy pathway. This study provides novel insights into a mechanism whereby Cav1 translocates from a normal plasma membrane distribution to an inverted secreted form implicated in PCa disease progression.