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

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.

Farnesoid X receptor activation induces antitumour activity in colorectal cancer by suppressing JAK2/STAT3 signalling via transactivation of SOCS3 gene

“…The highly malignant behaviour of colon cancer cells is closely associated with the activity of JAK/STAT pathway. 35 Our data indicated that OCA treatment repressed the activation of JAK2/STAT3 pathway in colon cancer cells, which was further confirmed by IF staining, showing increased levels of STAT3 protein located in the cell cytoplasm. In addition, restoration of JAK2/STAT3 signalling by colivelin and IL-6 abolished OCA-mediated proliferation and invasion inhibition.…”

Extracellular Vesicles in HTLV-1 Communication: The Story of an Invisible Messenger

“…These EVs are taken up by the same cells (i.e., in autocrine feedback loop), and are able to affect their growth and survival in a time- and concentration-dependent manner [ 114 ]. In addition, Ren et al 2019 found that EVs derived from colon cancer cells accelerated cell division, which in turn contributed to disease progression [ 124 ]. Another study examining gastric cancer EVs also found increased cell proliferation in a time and concentration manner through activation of Akt and ERK, and PI3k pathways [ 125 ].…”

Roles of exosomes in diagnosis and treatment of colorectal cancer

“…Moreover, Ren et al [ 31 ] have reported that self-growth or proliferation through exosome secretion, especially under hypoxic conditions, by reduction of the mitosis and activation duration can be promoted by CRC cells. In a recent study, the CRC cell-derived exosomes are separated from human colon cancer cell line SW480 and HCT116.…”