In vivo validation of carcinogenic effects of cancer cell-derived extracellular vesicles

Abstract

The present study investigated whether tumor cell-derived exosomes initiate DNA damage through communication with normal cells or are involved in the metastasis cascade of cancer cells. Cancer cell-derived exosomes (exosome-mimics) were artificially produced as follows: cultured hepatoma cell line hep3B was sequentially passed through 10, 5 and 1.0 μm filters using a mini extruder to experimentally produce 30-200 μm exosome-mimics. Size was confirmed and images were obtained. Peritoneums of the experimental group were infected with exosome-mimics for 4 weeks in normal BALB/c nude mice once (0.1mL, 1.0 × 105cells)/day. The control group received intraperitoneal culture medium. The other experimental group was administered subcutaneous tumor cells. Injection of exosome-mimics was found to be involved in the development and metastasis of cancer. Serum α- fetoprotein (AFP) was significantly increased in exosome-mimic and tumor cell-treated groups compared to control group. In addition, the expression of cancer-related factors (p53, p21, bcl-2, Ki-67, heat shock protein 70 (Hsp70) and Glypican 3 (GPC3)) in the exosome-mimic treated group had the same pattern as the tumor cell-treated group. In conclusion, cancer cell-derived exosomes were thought to be involved in cancer development and metastasis.

Key words: Cancer cell-derived exosome, Cancer metastasis, Exosome-mimics.