109682 20230519145530.0 doi 10.1016/j.jlr.2021.100109 sideral 126986 ART-2021-126986 eng Contursi, A Platelets induce free and phospholipid-esterified 12-hydroxyeicosatetraenoic acid generation in colon cancer cells by delivering 12-lipoxygenase 2021 Access copy available to the general public Unrestricted Platelets promote tumor metastasis by inducing promalignant phenotypes in cancer cells and directly contributing to cancer-related throm-botic complications. Platelet-derived extracellular vesicles (EVs) can promote epithelial-mesenchymal transition (EMT) in cancer cells, which confers high-grade malignancy. 12S-hydroxyeicosatetraenoic acid (12-HETE) generated by platelet-type 12-lipoxygenase (12-LOX) is considered a key modulator of cancer metastasis through unknown mechanisms. In plate-lets, 12-HETE can be esterified into plasma membrane phospholipids (PLs), which drive thrombosis. Using cocultures of human platelets and human colon adenocarcinoma cells (line HT29) and LC-MS/MS, we investigated the impact of platelets on cancer cell biosynthesis of 12S-HETE and its esterification into PLs and whether platelet ability to transfer its mo-lecular cargo might play a role. To this aim, we performed coculture experiments with CFSE[5-(and-6)-carboxyfluorescein diacetate, succinimidyl ester]-loaded platelets. HT29 cells did not generate 12S-HETE or express 12-LOX. However, they ac-quired the capacity to produce 12S-HETE mainly esterified in plasmalogen phospholipid forms following the uptake of platelet-derived medium-sized EVs (mEVs) expressing 12-LOX. 12-LOX was detected in plasma mEV of patients with adenomas/ adenocarcinomas, implying their potential to deliver the protein to cancer cells in vivo. In cancer cells exposed to platelets, endogenous but not exogenous 12S-HETE contributed to changes in EMT gene expression, mitigated by three structurally unrelated 12-LOX inhibitors. In conclusion, we showed that platelets induce the generation of primarily esteri-fied 12-HETE in colon cancer cells following mEV-mediated delivery of 12-LOX. The modification of cancer cell phospholipids by 12-HETE may functionally impact cancer cell biology and represent a novel target for anticancer agent development. info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI14-01218 info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 6.676 2021 BIOCHEMISTRY & MOLECULAR BIOLOGY 60 / 297 = 0.202 2021 Q1 T1 1.817 2021 Cell Biology 2021 Q1 Biochemistry 2021 Q1 11.0 2021 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Schiavone, S Dovizio, M Hinz, C Fullone, R Tacconelli, S Tyrrell, VJ Grande, R Lanuti, P Marchisio, M Zucchelli, M Ballerini, P Lanas Arbelola, A Universidad de Zaragoza (orcid)0000-0001-5932-2889 O''Donnell, VB Patrignani, P 1007 610 Universidad de Zaragoza Dpto. Medicina, Psiqu. y Derm. Area Medicina 62 (2021), 100109 [18 pp] J. lipid res. Journal of Lipid Research 0022-2275 3324330 http://zaguan.unizar.es/record/109682/files/texto_completo.pdf Versión publicada 3445783 http://zaguan.unizar.es/record/109682/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:109682 articulos driver 2023-05-18-15:29:28 ARTICLE