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It has been well\u2010established that cancer cells themselves can induce cachexia via the release of several pro\u2010cachectic and pro\u2010inflammatory factors. However, it is unclear how this process is regulated and the key cachexins that are involved. In this study, we validated C26 and EL4 as cachexic and non\u2010cachexic cell models, respectively. Treatment of adipocytes and myotubes with C26 conditioned medium induced lipolysis and atrophy, respectively. We profiled soluble secreted proteins (secretome) as well as small extracellular vesicles (sEVs) released from cachexia\u2010inducing (C26) and non\u2010inducing (EL4) cancer cells by label\u2010free quantitative proteomics. A total of 1268 and 1022 proteins were identified in the secretome of C26 and EL4, respectively. Furthermore, proteomic analysis of sEVs derived from C26 and EL4 cancer cells revealed a distinct difference in the protein cargo. Functional enrichment analysis using FunRich highlighted the enrichment of proteins that are implicated in biological processes such as muscle atrophy, lipolysis, and inflammation in both the secretome and sEVs derived from C26 cancer cells. Overall, our characterisation of the proteomic profiles of the secretory factors and sEVs from cachexia\u2010inducing and non\u2010inducing cancer cells provides insights into tumour factors that promote weight loss by mediating protein and lipid loss in various organs and tissues. Further investigation of these proteins may assist in highlighting potential therapeutic targets and biomarkers of cancer cachexia.<\/jats:p>","DOI":"10.1002\/pmic.202100314","type":"journal-article","created":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T05:25:36Z","timestamp":1686633936000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Proteomic analysis of the small extracellular vesicles and soluble secretory proteins from cachexia inducing and non\u2010inducing cancer cells"],"prefix":"10.1002","volume":"23","author":[{"given":"Sai V.","family":"Chitti","sequence":"first","affiliation":[{"name":"Department of Biochemistry La Trobe Institute for Molecular Science La Trobe University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeyoung","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry La Trobe Institute for 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