Against cancer metastasis by targeting extracellular vesicles by precise antibodies Nao Nishida-Aoki1, Naoomi Tominaga1, Fumitaka Takeshita2, Hikaru Sonoda1, Yusuke Yoshioka1 and Takahiro Ochiya1 Division of Molecular and Cellular Medicine, National Cancer Centre Aurora C Synonyms Investigation Institute, Japan; 2Department of Functional Evaluation, FIOC, National Cancer Centre Study Institute, JapanOT1.Exosome-SIRPalpha, a CD47 blockade increases cancer cell phagocytosis Eunee Koh1, Yoosoo Yang2 and In-San Kim1 KU-KIST Graduate College of Converging Science and Technology, Seoul, Republic of Korea; 2Korea Institute of Science and Technology, Seoul, Republic of KoreaIntroduction: Cancer-derived extracellular vesicles (EVs) promote metastasis by forming cancer microenvironment and pre-metastatic niche. Thus, inhibiting the pro-metastatic function of cancerderived EVs is anticipated to suppress metastasis. We demonstrated the therapeutic notion of targeting EVs working with an experimental model. Techniques: The antibodies certain to human CD9 and human CD63 had been injected intravenously for every three days for any total of 3 instances to an orthotropic mice model of highly-metastatic human breast cancer. Immediately after 35 days, the metastasis levels were evaluated by ex vivo imaging and immunohistochemistry. The EVs collected by ultracentrifugation from filtrated culture media were stained by a lipophilic dye PKH67 or DiR. To transiently get rid of mouse innate macrophages, clodronate liposomes have been injected intravenously five days prior to the administration of your EVs. Outcomes: The species-specificity and also the binding potential around the surface of your EVs in the human breast cancer cells on the antibodies were confirmed. Antibody therapy drastically lowered lung metastasis compared to the control IgG therapy. The antibodies didn’t reduce the size from the primary tumours, cell proliferation and invasion abilities, but decreased the level of circulating cancer-derived EVs. These observations recommended that the antibodies suppressed metastasis by disrupting the EVs but not main tumours. Indeed, the antibodies stimulated removal of EVs by macrophages both in vitro and in vivo. The stimulation of EV removal disappeared by depletion of innate macrophages of mice, indicating that the stimulation of removal with the EVs was macrophage-dependent. Conclusion: Recognition with the cancer-derived EVs by antibodies suppressed lung metastasis, by stimulating the removal from the EVs by macrophages. Identifying the particular targets in the surface from the cancer-derived EVs is necessary for sensible use.CD47, a “don’t eat me” signal, is over-expressed around the surface of most tumours that interacts with signal regulatory protein (SIRP) on phagocytic cells. By engaging SIRP, CD47 limits the ability ofReference 1. Nishida-Aoki et al., Mol. Ther. 2017; 25: 18191.Thursday May 18,Room: Metropolitan Ballroom East Symposium Session 2 Platelets, Coagulation, and Inflammation Chairs: Eric Boilard and Pia Sijander 11:002:30 p.m.OT2.Extracellular vesicles from activated platelets: a quantitative cryoelectron microscopy and immuno-gold labelling study Alain R. Brisson1, Sisareuth Tan1, Celine Gounou1, Romain Linares1, Nicolas Arraud1 and Stephane Mornet1 UMR-5248 CNRS University of Bordeaux, Bordeaux, CaSR list France; 2UPRICMCB CNRSIntroduction: Upon activation, blood platelets release two forms of extracellular vesicles (EV), namely microparticles characterised by the presence at their surface of phosphatidylserine (PS), whi.
