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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

118 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)181-191
Number of pages11
JournalMolecular Therapy
Volume25
Issue number1
DOIs
Publication statusPublished - 2017 Jan 4
Externally publishedYes

Keywords

  • breast cancer
  • CD63
  • CD9
  • exosome
  • extracellular vesicles
  • metastasis
  • therapeutic antibody

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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