| Abstract |
The abundance of circulating plasma small extracellular vesicles (sEVs) has been reported to be elevated in cancer; however, the underlying mechanism remains unclear. In this study, a pharmacokinetic approach was used to determine the factors contributing to elevated plasma sEV levels during cancer in a tumor-bearing mouse model. Mouse plasma-derived sEVs (MP-sEVs) isolated from tumor-bearing mice showed increased protein concentrations and physicochemical characteristics comparable to MP-sEVs isolated from healthy mice. The steady-state concentration of sEVs is determined by the balance between the MP-sEV production and clearance. Thus, to determine whether tumorigenesis influences sEV clearance, isolated MP-sEVs were intravenously administered to either tumor-bearing or healthy mice. The results showed minimal differences in sEV clearance rates, suggesting that sEV production is the driving force of elevated MP-sEV concentrations. Lastly, CD63-gLuc stably expressing B16BL6-bearing mice were used to estimate the contribution of tumor cell-derived sEVs in the plasma. The gLuc activity of the MP-sEVs isolated was below the limit of detection, and it was estimated that the tumor cell-derived sEVs comprised at most 0.5% of the total MP-sEVs. Taken together, these results suggest that cells other than tumor cells contribute to elevated plasma sEV levels in cancer.
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