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Cancer Alters the Metabolic Fingerprint of Extracellular Vesicles

Hanhineva Kati; Tavukcuoglu Zeynep; Palviainen Mari; Velagapudi Vidya; Ranki Annamari; Siljander Pia; Auriola Seppo; Kärkkäinen Olli; Laukkanen Kirsi

dc.contributor.authorHanhineva Kati
dc.contributor.authorTavukcuoglu Zeynep
dc.contributor.authorPalviainen Mari
dc.contributor.authorVelagapudi Vidya
dc.contributor.authorRanki Annamari
dc.contributor.authorSiljander Pia
dc.contributor.authorAuriola Seppo
dc.contributor.authorKärkkäinen Olli
dc.contributor.authorLaukkanen Kirsi
dc.date.accessioned2022-10-28T12:29:25Z
dc.date.available2022-10-28T12:29:25Z
dc.identifier.urihttps://www.utupub.fi/handle/10024/159871
dc.description.abstractSimple SummaryCancer changes cell metabolism. In this study, we explored if the metabolic rewiring also alters the metabolite content of cancer-derived extracellular vesicles (EVs). For this, metabolomes of EVs from different cancers (prostate, cutaneous T-cell lymphoma, and colon cancer cell lines) were compared with the metabolomes of control EVs derived from matched non-cancerous cell lines. The metabolomes of EVs from all three cancer types significantly differed from their respective control EVs by elevated levels of proline and succinate. Additionally, prostate and cutaneous T-cell lymphoma cell line -derived EVs contained elevated levels of creatinine and folate when compared to controls. In conclusion, this study presents the first evidence that a shared panel of metabolites in EVs reflects the altered metabolic state of multiple cancer cell types in vitro. These results warrant further studies of the significance and usability of a metabolic fingerprint in cancer studies and for biomarker discovery.Cancer alters cell metabolism. How these changes are manifested in the metabolite cargo of cancer-derived extracellular vesicles (EVs) remains poorly understood. To explore these changes, EVs from prostate, cutaneous T-cell lymphoma (CTCL), colon cancer cell lines, and control EVs from their noncancerous counterparts were isolated by differential ultracentrifugation and analyzed by nanoparticle tracking analysis (NTA), electron microscopy (EM), Western blotting, and liquid chromatography-mass spectrometry (LC-MS). Although minor differences between the cancerous and non-cancerous cell-derived EVs were observed by NTA and Western blotting, the largest differences were detected in their metabolite cargo. Compared to EVs from noncancerous cells, cancer EVs contained elevated levels of soluble metabolites, e.g., amino acids and B vitamins. Two metabolites, proline and succinate, were elevated in the EV samples of all three cancer types. In addition, folate and creatinine were elevated in the EVs from prostate and CTCL cancer cell lines. In conclusion, we present the first evidence in vitro that the altered metabolism of different cancer cells is reflected in common metabolite changes in their EVs. These results warrant further studies on the significance and usability of this metabolic fingerprint in cancer.
dc.language.isoen
dc.publisherMDPI
dc.titleCancer Alters the Metabolic Fingerprint of Extracellular Vesicles
dc.identifier.urnURN:NBN:fi-fe2021042824821
dc.relation.volume12
dc.contributor.organizationfi=PÄÄT Elintarvikekemia ja elintarvikekehitys|en=PÄÄT Food Chemistry and Food Development|
dc.contributor.organization-code2606204
dc.converis.publication-id51356620
dc.converis.urlhttps://research.utu.fi/converis/portal/Publication/51356620
dc.identifier.eissn2072-6694
dc.identifier.jour-issn2072-6694
dc.okm.affiliatedauthorHanhineva, Kati
dc.okm.discipline1182 Biokemia, solu- ja molekyylibiologiafi_FI
dc.okm.discipline1182 Biochemistry, cell and molecular biologyen_GB
dc.okm.internationalcopublicationnot an international co-publication
dc.okm.internationalityInternational publication
dc.okm.typeJournal article
dc.publisher.countrySveitsifi_FI
dc.publisher.countrySwitzerlanden_GB
dc.publisher.country-codeCH
dc.relation.articlenumberARTN 3292
dc.relation.doi10.3390/cancers12113292
dc.relation.ispartofjournalCancers
dc.relation.issue11
dc.year.issued2020


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