Intercellular transfer of messenger RNAs in multiorgan tumorigenesis by tumor cell-derived exosomes.

Abstract

Exosomes are small membrane vesicles of endocytic origin. They are derived from various cells, including tumor cells, and may serve as important modulators of intercellular communication. The present study established a U‑87MG human glioblastoma cell line that showed a stable expression of green fluorescent protein (GFP; U‑87‑GFP). Two types of human tumor cell lines, U‑87‑GFP and LoVo human colon cancer cells, were demonstrated to communicate through the transfer of GFP messenger (m)RNA by exosomes. Furthermore, GFP mRNAs delivered by the U‑87‑GFP cell‑derived exosomes were translated into functional proteins in the recipient LoVo cells. In addition, LoVo cells were demonstrated to uptake exosomes derived from the U‑87‑GFP cells by clathrin‑mediated endocytosis. These results indicate that tumor cell‑derived exosomes may represent vesicular carriers that regulate gene expression, which may provide a pathway of intercellular communication in the tumor microenvironment during multiorgan tumorigenesis. The exosome uptake pathway may have potential therapeutic applications in multiorgan tumorigenesis.