Extruded small extracellular vesicles: splinters of circulating tumour cells may promote cancer metastasis?

Researchers at Binghamton University speculate ruptured circulating tumour cells (CTC) in capillaries could release a large number of small extracellular vesicle-like vesicles, namely mechanically extruded sEV (sEV^me), which can encapsulate chromosomal DNA fragments. These sEV^me have similar physicochemical properties compared to small extracellular vesicles spontaneously secreted by living cells (sEV^ss), and thus sEV^me and sEV^ss cannot be effectively distinguished based on their size or membrane protein markers. Meanwhile, these sEV^me derived from CTC inherit oncogenic payloads, deliver cargo through the bloodstream to recipient cells, and thus may promote cancer metastasis. The validation of this speculation could facilitate our understanding of EV biogenesis and cancer pathology. The potential finding will also provide a theoretical foundation for burgeoning liquid biopsy using DNA fragments derived from harvested sEV.

Proposed sEV^me generation by CTC

a Release of sEV^me by arrested MDA-MB-231 breast cancer cells in microchannels mimicking capillaries (microchannel width: 10 µm; length: 600 µm; pressure: 15 mmHg). b Transmission Electron Microscopy (TEM) image of sEV^me produced by arrested MDA-MB-231 cells in microchannels (microchannel width: 10 µm; length: 600 µm; pressure: 15 mmHg), which exhibits characteristic saucer-shaped morphology. c Structured Illumination Microscopy (SEM) image of sEV^me produced by arrested GFP MDA-MB-231 cells in microchannels. Fluorescence: red: DID, membrane label; green: GFP, cytoplasm label; blue: Hoechst 33342, DNA label. d TEM image of sEV^ss harvested from cell culture supernatant of MDA-MB-231 cells, which also exhibits characteristic saucer-shaped morphology. e Illustration of releasing sEV^me by arrested CTC in capillaries.