Cancer exosome tropism could provide useful information for future cancer therapeutic applications

Exosomes, a subtype of extracellular vesicles, ranging from 50 to 200 nm in diameter, and mediate cell-to-cell communication in normal biological and pathological processes. Exosomes derived from tumors have multiple functions in cancer progression, resistance, and metastasis through cancer exosome-derived tropism. However, there is no quantitative information on cancer exosome-derived tropism. Such data would be highly beneficial to guide cancer therapy by inhibiting exosome release and/or uptake. Using two fluorescent protein (mKate2) transfected ovarian cancer cell lines (OVCA4 and OVCA8), researchers from the University of Oklahoma Health Sciences Center quantified cancer exosome tropism by measuring the released exosome from ovarian cancer cells and determining the uptake of exosomes into parental ovarian cancer cells, 3D spheroids, and tumors in tumor-bearing mice. The OVCA4 cells release 50 to 200 exosomes per cell, and the OVCA8 cells do 300 to 560 per cell. The uptake of exosomes by parental ovarian cancer cells is many-fold higher than by non-parental cells. In tumor-bearing mice, most exosomes are homing to the parent cancer rather than other tissues. The researchers successfully quantified exosome release and uptake by the parent cancer cells, further proving the tropism of cancer cell-derived exosomes. The results implied that cancer exosome tropism could provide useful information for future cancer therapeutic applications.

Diagram of cancer therapeutic application using tumor-derived exosome tropism

(A) Ovarian cancer cells secrete exosomes to the extracellular matrix or culture media. These fluorescent exosomes can home to their parental ovarian cancer cells or to 3D spheroids through cancer cell exosome tropism, which promotes tumor growth. (B) Thus, inhibition of tumor exosome release by the exosome inhibitors could suppress tumor growth prevented by tumor exosome tropism. (C) Additionally, potentially, tumor exosome-targeted therapies (green diamond, e.g., exosome-targeted drug delivery systems) could form exosome-therapy complexes, and they are inclined to home to parent cancer cells through tropism and deliver a significant number of therapies to the tumor. Then, finally, it causes to inhibit tumor growth. Thus, a tumor exosome-targeted therapeutic system could be another avenue of drug delivery system as a cancer therapy.

Ren X, Kang C, Garcia-Contreras L, Kim D. (2023) Understanding of Ovarian Cancer Cell-Derived Exosome Tropism for Future Therapeutic Applications. Int J Mol Sci 24(9):8166. [article]

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