期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/ncomms14470
关键词
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资金
- Japan Science and Technology Agency (JST)
- Basic Science and Platform Technology Program for Innovative Biological Medicine
- Project for Development of Innovative Research on Cancer Therapeutics (P-Direct)
- Project for Cancer Research and Therapeutic Evolution (P-CREATE)
- National Cancer Center Research and Development Fund [26-A-3]
- Japan Agency for Medical Research and Development (AMED)
- Grants-in-Aid for Scientific Research [16K15704, 16H05472, 17H04338] Funding Source: KAKEN
Advanced ovarian cancers are highly metastatic due to frequent peritoneal dissemination, resulting in dismal prognosis. Here we report the functions of cancer-derived extracellular vesicles (EVs), which are emerging as important mediators of tumour metastasis. The EVs from highly metastatic cells strongly induce metastatic behaviour in moderately metastatic tumours. Notably, the cancer EVs efficiently induce apoptotic cell death in human mesothelial cells in vitro and in vivo, thus resulting in the destruction of the peritoneal mesothelium barrier. Whole transcriptome analysis shows that MMP1 is significantly elevated in mesothelial cells treated with highly metastatic cancer EVs and intact MMP1 mRNAs are selectively packaged in the EVs. Importantly, MMP1 expression in ovarian cancer is tightly correlated with a poor prognosis. Moreover, MMP1 mRNA-carrying EVs exist in the ascites of cancer patients and these EVs also induce apoptosis in mesothelial cells. Our findings elucidate a previously unknown mechanism of peritoneal dissemination via EVs.
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