Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer

Akira Yokoi, Yusuke Yoshioka, Yusuke Yamamoto, Mitsuya Ishikawa, Shun-ichi Ikeda, Tomoyasu Kato, Tohru Kiyono, Fumitaka Takeshita, Hiroaki Kajiyama, Fumitaka Kikkawa and Takahiro Ochiya ()
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Akira Yokoi: National Cancer Center Research Institute
Yusuke Yoshioka: National Cancer Center Research Institute
Yusuke Yamamoto: National Cancer Center Research Institute
Mitsuya Ishikawa: National Cancer Center Hospital
Shun-ichi Ikeda: National Cancer Center Hospital
Tomoyasu Kato: National Cancer Center Hospital
Tohru Kiyono: National Cancer Center Research Institute
Fumitaka Takeshita: Fundamental Innovative Oncology Core Center (FIOC), National Cancer Center Research Institute
Hiroaki Kajiyama: Nagoya University Graduate School of Medicine
Fumitaka Kikkawa: Nagoya University Graduate School of Medicine
Takahiro Ochiya: National Cancer Center Research Institute

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms14470

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