Disruption of Circulating Extracellular Vesicles as a Novel Therapeutic Strategy against Cancer Metastasis

Nao Nishida-Aoki, Naoomi Tominaga, Fumitaka Takeshita, Hikaru Sonoda, Yusuke Yoshioka, Takahiro Ochiya*

*この研究の対応する著者

研究成果: Article査読

125 被引用数 (Scopus)

抄録

Metastasis is the main cause of cancer mortality for many types of cancer; however, difficulties remain in effectively preventing metastasis. It has been recently and widely reported that cancer-derived extracellular vesicles (EVs) contribute to cancer metastasis. Thus, therapeutic strategies targeting cancer-derived EVs hold great promise because of the possibility of EVs driving the cancer microenvironment toward metastasis. Here, we provide a novel strategy for therapeutic antibody treatment to target cancer-derived EVs and inhibit the metastasis of breast cancer in a mouse model, establishing a rationale for further clinical investigation. Treatment with human-specific anti-CD9 or anti-CD63 antibodies significantly decreased metastasis to the lungs, lymph nodes, and thoracic cavity, although no obvious effects on primary xenograft tumor growths were observed. In in vitro and in vivo experiments, the EVs incubated with the targeted antibodies were preferentially internalized by macrophages, suggesting that antibody-tagged cancer-derived EVs would be eliminated by macrophages. Our results suggested that therapeutic antibody administration effectively suppresses EV-triggered metastasis in cancer and that the removal of EVs could be a novel strategy for cancer therapy.

本文言語English
ページ(範囲)181-191
ページ数11
ジャーナルMolecular Therapy
25
1
DOI
出版ステータスPublished - 2017 1月 4
外部発表はい

ASJC Scopus subject areas

  • 分子医療
  • 分子生物学
  • 遺伝学
  • 薬理学
  • 創薬

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