Back to Search
Start Over
Colorectal cancer-derived small extracellular vesicles establish an inflammatory premetastatic niche in liver metastasis.
- Source :
-
Carcinogenesis . Nov2018, Vol. 39 Issue 11, p1368-1379. 12p. - Publication Year :
- 2018
-
Abstract
- Liver metastases develop in more than half of the patients with colorectal cancer (CRC) and are associated with a poor prognosis. The factors influencing liver metastasis of CRC are poorly characterized, but this information is urgently needed. We have now discovered that small extracellular vesicles (sEVs; exosomes) derived from CRC can be specifically targeted to liver tissue and induce liver macrophage polarization toward an interleukin-6 (IL-6)-secreting proinflammatory phenotype. More importantly, we found that microRNA-21-5p (miR-21) was highly enriched in CRC-derived sEVs and was essential for creating a liver proinflammatory phenotype and liver metastasis of CRC. Silencing either miR-21 in CRC-sEVs or Toll-like receptor 7 (TLR7) in macrophages, to which miR-21 binds, abolished CRC-sEVs' induction of proinflammatory macrophages. Furthermore, miR-21 expression in plasma-derived sEVs was positively correlated with liver metastasis in CRC patients. Collectively, our data demonstrate a pivotal role of CRC-sEVs in promoting liver metastasis by inducing an inflammatory premetastatic niche through the miR-21–TLR7–IL-6 axis. Thus, sEVs–miR-21 represents a potential prognostic marker and therapeutic target for CRC patients with liver metastasis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01433334
- Volume :
- 39
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 133582654
- Full Text :
- https://doi.org/10.1093/carcin/bgy115