Colon cancer cells secrete exosomes to promote self-proliferation by shortening mitosis duration and activation of STAT3 in a hypoxic environment

Abstract

Abstract Colon-cancer-cell-derived exosomes (CDEs) are emerging mediators of tumorigenesis and serve as messengers of intercellular communication; however, whether the CDEs affect the proliferation of colon cancer cells themselves remains unknown. In the current study, the CDEs isolated from human colon cancer cell line SW480 and HCT116 showed a size range of 60–150 nm, typical bilayer-encapsulated vesicles, and expressed the exosomal markers CD81 and CD63. Incubation of SW480 cells with CDEs labelled with PKH67 fluorescent markers revealed that SW480 cells were able to absorb CDEs, which were mostly distributed around the nucleus. Hypoxic conditions promoted colon cancer cells to release a greater number of CDEs than normoxic conditions. MTT cell proliferation assay demonstrated CDEs promoted the proliferation of colon cancer cells in a time- and dose-dependent manner. Mechanistically, CDEs promoted colon cancer cell growth mainly through shortening mitosis duration. Meanwhile, the levels of phosphorylated STAT3 in colon cancer cells was up-regulated with the treatment of CDEs derived from hypoxic tumor cells. Our data suggests that colon cancer cells are able to promote self-growth through the secretion of exosomes, especially under hypoxic conditions, which shortens mitosis duration and activates STAT3.

Keywords

• Exosomes
• Hypoxia
• Cell proliferation
• Mitosis
• STAT3