000109682 001__ 109682
000109682 005__ 20230519145530.0
000109682 0247_ $$2doi$$a10.1016/j.jlr.2021.100109
000109682 0248_ $$2sideral$$a126986
000109682 037__ $$aART-2021-126986
000109682 041__ $$aeng
000109682 100__ $$aContursi, A
000109682 245__ $$aPlatelets induce free and phospholipid-esterified 12-hydroxyeicosatetraenoic acid generation in colon cancer cells by delivering 12-lipoxygenase
000109682 260__ $$c2021
000109682 5060_ $$aAccess copy available to the general public$$fUnrestricted
000109682 5203_ $$aPlatelets 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.
000109682 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI14-01218
000109682 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000109682 590__ $$a6.676$$b2021
000109682 592__ $$a1.817$$b2021
000109682 594__ $$a11.0$$b2021
000109682 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b60 / 297 = 0.202$$c2021$$dQ1$$eT1
000109682 593__ $$aCell Biology$$c2021$$dQ1
000109682 593__ $$aBiochemistry$$c2021$$dQ1
000109682 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000109682 700__ $$aSchiavone, S
000109682 700__ $$aDovizio, M
000109682 700__ $$aHinz, C
000109682 700__ $$aFullone, R
000109682 700__ $$aTacconelli, S
000109682 700__ $$aTyrrell, VJ
000109682 700__ $$aGrande, R
000109682 700__ $$aLanuti, P
000109682 700__ $$aMarchisio, M
000109682 700__ $$aZucchelli, M
000109682 700__ $$aBallerini, P
000109682 700__ $$0(orcid)0000-0001-5932-2889$$aLanas Arbelola, A$$uUniversidad de Zaragoza
000109682 700__ $$aO''Donnell, VB
000109682 700__ $$aPatrignani, P
000109682 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000109682 773__ $$g62 (2021), 100109 [18 pp]$$pJ. lipid res.$$tJournal of Lipid Research$$x0022-2275
000109682 8564_ $$s3324330$$uhttps://zaguan.unizar.es/record/109682/files/texto_completo.pdf$$yVersión publicada
000109682 8564_ $$s3445783$$uhttps://zaguan.unizar.es/record/109682/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000109682 909CO $$ooai:zaguan.unizar.es:109682$$particulos$$pdriver
000109682 951__ $$a2023-05-18-15:29:28
000109682 980__ $$aARTICLE