Colorectal cancer cell-derived exosomes promote proliferation and decrease apoptosis by activating the ERK pathway

Int J Clin Exp Pathol. 2019 Jul 1;12(7):2485-2495. eCollection 2019.

Abstract

Exosomes are small microvesicles released by various cells that play important roles in cell-cell communication. Numerous studies show that colorectal cancer (CRC) cell-derived exosomes are involved in the progression of CRC. However, the specific ways and mechanisms of action have not yet been fully clarified. In the present study, we found that, compared to normal colon epithelial cell (NCM460) derived exosomes, CRC cell-Lovo derived exosomes (Lovo-exo) could be more easily taken up by Lovo cells, most likely because of their cell tropism. In addition, Lovo-exo promoted Lovo cell proliferation and inhibited apoptosis, which is associated with an increased activation of the extracellular signal-regulated protein kinase (ERK). Lovo-exo also dramatically increased Lovo tumor cell growth in vivo. Moreover, the intratumoral injection of GW4869 (an exosomes inhibitor) suppressed tumor growth. These results indicate that CRC cell Lovo-derived exosomes may be a messenger for the proliferation requirements of the originating cancer cells, and targeting tumor-derived exosomes may be very promising for tumor treatment.

Keywords: Colorectal cancer; ERK; exosomes; tumor growth.