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dc.contributor.authorBerzaghi, Rodrigo
dc.contributor.authorIslam, Md Ashraful
dc.contributor.authorHellevik, Turid
dc.contributor.authorMartinez-Zubiaurre, Inigo
dc.date.accessioned2021-09-30T08:44:47Z
dc.date.available2021-09-30T08:44:47Z
dc.date.issued2021-04-24
dc.description.abstractReciprocal communication between the malignant and non-malignant cellular elements in tumors is essential for cancer sustainability and plays an important role in the response of cancers to treatments. Some of this cellular crosstalk takes place via secretion of vesicles that are actively released into the extracellular space by most cell types in tumors. Recent studies have demonstrated radiation-induced changes in the secretion rate and composition of extracellular vesicles (EVs), with impact on radiation-related cellular communication. However, little is known about the effects of different radiation regimens on the release of EVs by cells of the tumor microenvironment. In this study, we provide a comprehensive molecular characterization of EVs released by cultured primary lung tumor fibroblasts. We explore the quantitative and morphological changes triggered by ionizing radiation (IR), delivered as a single dose of 18 Gy or three consecutive daily medium-doses of 6 Gy. Cancer-associated fibroblasts (CAFs) secrete EVs with sizes ranging from 80 to 200 nm, expressing some of the classical exosome markers. Exposing CAFs to a single-high radiation dose (1 × 18 Gy) or fractionated medium-dose did not alter the release of CAF-EVs. The protein composition of CAF-EVs was analyzed by LC-MS/MS proteomics and revealed that CAF-EVs are enriched with heat shock proteins, integrins, tetraspanins, proteinases, collagens, growth factors and an array of molecules involved in the regulation of cell migration and the immune system. Quantitative proteomic analyses revealed minor changes in the protein composition of CAF-EVs after radiation exposure. Taken together, this study presents original data on lung tumor CAF-EV composition and reveals that release and protein cargo of CAF-EVs are largely unaltered after exposing CAFs to IR.en_US
dc.identifier.citationBerzaghi RB, Islam A, Hellevik T, Martinez IZ. Secretion rates and protein composition of extracellular vesicles released by cancer-associated fibroblasts after radiation. Journal of radiation research. 2021en_US
dc.identifier.cristinIDFRIDAID 1894901
dc.identifier.doi10.1093/jrr/rrab018
dc.identifier.issn0449-3060
dc.identifier.issn1349-9157
dc.identifier.urihttps://hdl.handle.net/10037/22686
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.relation.journalJournal of radiation research
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700en_US
dc.subjectVDP::Medisinske Fag: 700en_US
dc.titleSecretion rates and protein composition of extracellular vesicles released by cancer-associated fibroblasts after radiationen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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