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

We 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.