Era and Elke Pogge von Strandmannba Experimental Tumor Research, Center for Tumor Biology and Immunology, Clinic for Hematology, Oncology and Immunology, Philipps University of Marburg, Marburg, Cologne, Germany, Germany; bExperimental Tumor Study, Center for Tumor Biology and Immunology, Department of Hematology, Oncology and Immunology, Philipps University Marburg, Marburg, GermanySummary/Conclusion: Our findings give a conceptual advance in the understanding on the biogenesis and function of EVs, identifying BAG6 as an ESCRTassociated protein as well as a molecular switch for the formation of anti- versus pro-tumourigenic EVs in tumour Siglec-5/CD170 Proteins Storage & Stability immune surveillance.FA1.Improvement of a live-cell imaging approach for secretion Vitamin D Receptor Proteins Biological Activity activity of extracellular vesicles of person cells Yoshitaka Shirasakia, Keisuke Tsukadab, Nobutake Suzukic, Tamiko Minamisawad, Mai Yamagishie, Nobuyoshi Kosakaf, Takahiro Ochiyaf, Osamu Oharag, Kiyotaka Shibah and Sotaro UemuraiaIntroduction: Current studies have highlighted the function of melanoma cell-derived EVs within the formation of premetastatic niches or, around the contrary, in tumour immune surveillance. The molecular machinery and mechanisms directing distinct cargo loading, regulatory release and function of stress-induced EVs stay unknown. Techniques: EV release was quantified by NTA. EVs were isolated by ultracentrifugation and analysed by proteomics and transcriptomics. EV function was investigated in vivo by intravenous injections followed by lung transcriptomics and by utilizing an experimental metastasis transplantation model. The mechanistic release of EVs was analysed working with diverse molecular, cell biological, spectroscopic and microscopic strategies. Outcomes: Our study reveals a important role with the chaperone and NK cell ligand BAG6 for the formation and reprogramming of pro- and anti-tumour EVs. Loss of BAG6 led to an increase in EV production as well as a reduce in EV size. In contrast to the melanosomelike protein signature observed for WT-EVs, BAG6KOEVs showed an exosome-like profile and induced a neutrophil gene signature within the lungs of mice. Education with B-16V WT-EVs, but not BAG6KOEVs, suppressed lung metastasis concomittant with the accumulation of anti-tumour Ly6Clow patrolling monocytes. Mechanistically, the formation of antitumour EVs was dependent on BAG6 mediating the nucleo-cytoplasmic shuttling of CBP/p300 acetyltransferases to acetylate p53. We have identified a late endosomal P(S/T)AP motif in BAG6 which mediated its direct recruitment towards the ESCRT machinery, thereby delivering a molecular link in between the regulatory function of BAG6 to EV cargo loading.JST PRESTO, Tokyo, Japan; bThe University of Tokyo, bunkyo, Japan; cThe university of Tokyo, Bunkyo-ku, Japan; dJapanese Foundation For Cancer Study, Koto-ku, Japan; eDepartment of Biological Sciences, Graduate School of Science, The University of Tokyo, Japan; fDepartment of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Health-related University, Shinjyuku-ku, Japan; gRIKEN Institute for Integrative Medical Sciences, Yokohama, Japan; hJapaese Foundation for Cancer investigation, Tokyo, Japan; iThe University of Tokyo, Tokyo, JapanIntroduction: The cells in our physique exchange their details utilizing a variety of strategies to control the expression of functions, to type larger order systems and to sustain homeostasis. Especially in the communication between spatially separated cells, mediation of humoral components which include cytokines can be pointed out.
