Echanism by which EndoMT in EC produces EVs that could propagate angiostatic effects throughout the

Echanism by which EndoMT in EC produces EVs that could propagate angiostatic effects throughout the AT vasculature in obesity. Funding: NIHR15NHLBI, American Heart AssociationAIREA.ISEV2019 ABSTRACT BOOKSymposium Session 9: EV Biogenesis II Chairs: Bong Hwan Sung; Graca Raposo Location: Level B1, Hall B 17:008:OT09.Distinctive exosome subtypes have distinct ESCRT-associated biology and handle tumour cell adaptation in vivo Shih-Jung Fana, Benjamin Kroegerb, Pauline Mariea, Esther Bridgesa, Kristie McCormicka, John Masona, Helen Sheldona, Claudia Mendesa, Mark Wainwrighta, John Morrisa, Adrian Harrisa, Clive Wilsona and Deborah C I. Goberdhana University of Oxford, Oxford, UK; Melbourne, Australiaa bFunding: This function was funded by Cancer Study UK [C19591/A19076], the CRUK Oxford Centre Development Fund [C38302/A12278], BBSRC [BB/ K017462/1, BB/N016300/1, BB/R004862/1], John Fell Fund, Oxford, Wellcome Trust [MICRON; #091911, #107457], Royal College of Surgeons.Peter MacCallum Cancer Centre,OT09.Emerging function of L-type calcium channel-mediated calcium influx in regulating apoptotic bodies formation Thanh Kha Phana, Bo Shib, Niall Geogheganc, Kelly Rogersd and Ivan PooneaIntroduction: Figuring out the function of distinct extracellular vesicle (EV) and exosome subtypes has proved challenging, in part due to the difficulty in untangling the mechanisms leading to their generation. Techniques: We investigated the cell biology behind exosome formation utilizing the substantial endosomal compartments presented by an in vivo fly model, and analysis in human HCT116 along with other cancer cell lines. EV preparations have been also tested in vivo following injection in to human xenografts in mice. We analysed distinctive EV preparations by mass spectrometry utilizing Tandem Mass Tag TrkC Formulation labelling to identify modifications in protein cargo of EVs in response to microenvironmental stress. Final results: Applying these complementary approaches, we show that microenvironmental pressure, including glutamine depletion, leads to a switch in membrane trafficking from the classic late endosomal multivesicular endosomes to Rab11a-positive recycling endosomes as well as the production of Rab11a-positive exosomes, which promote cell growth below tension conditions. This activity is suppressed by blocking Rab11a-dependent trafficking and ESCRT function. Our proteomics and fly data recommend that some ESCRTs are differentially involved in these two exosome-generating processes. Additionally, mouse xenografts highlight roles for stress-induced EVs in growing the turnover of tumour cells, top to a rise in hypoxic tension, connected with selection for aggressive cells which will promote tumour progression. These stress-induced vesicles also possess a potent effect on blood vessel growth in vivo. Summary/Conclusion: We conclude that stressinduced EVs and exosomes made in Rab11a-positive recycling endosomes are involved in tumour adaptation.Division of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Australia; bDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia; cCentre for Dynamic Imaging, mGluR7 site Walter and Eliza Hall Institute of Medical Analysis, Melbourne, Australia; d Centre for Dynamic Imaging, Walter and Eliza Hall Institute of Medical Analysis, Melbourne, Australia; eLa Trobe University, Bundoora, AustraliaIntroduction: Dying cells typically break into smaller sized membrane-bound fragments, named apoptotic.