Platelets induce free and phospholipid-esterified 12-hydroxyeicosatetraenoic acid generation in colon cancer cells by delivering 12-lipoxygenase
Platelets promote tumor metastasis by inducing promalignant phenotypes in cancer cells and directly contributing to cancer-related thrombotic complications. Platelet-derived extracellular vesicles (EVs) can promote epithelial-mesenchymal transition (EMT) in cancer cells, which confers high-grade mal...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227521000912 |
| _version_ | 1819320375781097472 |
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| author | Annalisa Contursi Simone Schiavone Melania Dovizio Christine Hinz Rosa Fullone Stefania Tacconelli Victoria J. Tyrrell Rosalia Grande Paola Lanuti Marco Marchisio Mirco Zucchelli Patrizia Ballerini Angel Lanas Valerie B. O'Donnell Paola Patrignani |
| author_facet | Annalisa Contursi Simone Schiavone Melania Dovizio Christine Hinz Rosa Fullone Stefania Tacconelli Victoria J. Tyrrell Rosalia Grande Paola Lanuti Marco Marchisio Mirco Zucchelli Patrizia Ballerini Angel Lanas Valerie B. O'Donnell Paola Patrignani |
| author_sort | Annalisa Contursi |
| collection | DOAJ |
| description | Platelets promote tumor metastasis by inducing promalignant phenotypes in cancer cells and directly contributing to cancer-related thrombotic 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 platelets, 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 molecular 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 acquired 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 esterified 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. |
| first_indexed | 2024-12-24T11:18:35Z |
| format | Article |
| id | doaj.art-385ca02ae4ae423fb1579f73301dbf19 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-24T11:18:35Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-385ca02ae4ae423fb1579f73301dbf192022-12-21T16:58:18ZengElsevierJournal of Lipid Research0022-22752021-01-0162100109Platelets induce free and phospholipid-esterified 12-hydroxyeicosatetraenoic acid generation in colon cancer cells by delivering 12-lipoxygenaseAnnalisa Contursi0Simone Schiavone1Melania Dovizio2Christine Hinz3Rosa Fullone4Stefania Tacconelli5Victoria J. Tyrrell6Rosalia Grande7Paola Lanuti8Marco Marchisio9Mirco Zucchelli10Patrizia Ballerini11Angel Lanas12Valerie B. O'Donnell13Paola Patrignani14Department of Neuroscience, Imaging and Clinical Science, “G. d'Annunzio” University, Chieti, Italy; Center for Advanced Studies and Technology (CAST), “G. d'Annunzio” University, Chieti, ItalyDepartment of Neuroscience, Imaging and Clinical Science, “G. d'Annunzio” University, Chieti, Italy; Center for Advanced Studies and Technology (CAST), “G. d'Annunzio” University, Chieti, ItalyDepartment of Neuroscience, Imaging and Clinical Science, “G. d'Annunzio” University, Chieti, Italy; Center for Advanced Studies and Technology (CAST), “G. d'Annunzio” University, Chieti, ItalySystems Immunity Research Institute and Division of Infection and Immunity, School of Medicine Cardiff University, Cardiff, United KingdomDepartment of Neuroscience, Imaging and Clinical Science, “G. d'Annunzio” University, Chieti, Italy; Center for Advanced Studies and Technology (CAST), “G. d'Annunzio” University, Chieti, ItalyDepartment of Neuroscience, Imaging and Clinical Science, “G. d'Annunzio” University, Chieti, Italy; Center for Advanced Studies and Technology (CAST), “G. d'Annunzio” University, Chieti, ItalySystems Immunity Research Institute and Division of Infection and Immunity, School of Medicine Cardiff University, Cardiff, United KingdomDepartment of Neuroscience, Imaging and Clinical Science, “G. d'Annunzio” University, Chieti, Italy; Center for Advanced Studies and Technology (CAST), “G. d'Annunzio” University, Chieti, ItalyCenter for Advanced Studies and Technology (CAST), “G. d'Annunzio” University, Chieti, Italy; Department of Medicine and Aging Sciences, “G. d'Annunzio” University, Chieti, ItalyCenter for Advanced Studies and Technology (CAST), “G. d'Annunzio” University, Chieti, Italy; Department of Medicine and Aging Sciences, “G. d'Annunzio” University, Chieti, ItalyCenter for Advanced Studies and Technology (CAST), “G. d'Annunzio” University, Chieti, ItalyDepartment of Neuroscience, Imaging and Clinical Science, “G. d'Annunzio” University, Chieti, Italy; Department of Innovative Technologies in Medicine and Dentistry, “G. d'Annunzio” University, Chieti, ItalyUniversity Hospital LB, Aragon Health Research Institute (IISAragon), CIBERehd, University of Zaragoza, Zaragoza, SpainSystems Immunity Research Institute and Division of Infection and Immunity, School of Medicine Cardiff University, Cardiff, United KingdomDepartment of Neuroscience, Imaging and Clinical Science, “G. d'Annunzio” University, Chieti, Italy; Center for Advanced Studies and Technology (CAST), “G. d'Annunzio” University, Chieti, Italy; For correspondence: Paola PatrignaniPlatelets promote tumor metastasis by inducing promalignant phenotypes in cancer cells and directly contributing to cancer-related thrombotic 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 platelets, 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 molecular 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 acquired 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 esterified 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.http://www.sciencedirect.com/science/article/pii/S0022227521000912blood platelets12-HETE12-Lipoxygenaseextracellular vesiclescolorectal cancerplasma membrane phospholipids |
| spellingShingle | Annalisa Contursi Simone Schiavone Melania Dovizio Christine Hinz Rosa Fullone Stefania Tacconelli Victoria J. Tyrrell Rosalia Grande Paola Lanuti Marco Marchisio Mirco Zucchelli Patrizia Ballerini Angel Lanas Valerie B. O'Donnell Paola Patrignani Platelets induce free and phospholipid-esterified 12-hydroxyeicosatetraenoic acid generation in colon cancer cells by delivering 12-lipoxygenase Journal of Lipid Research blood platelets 12-HETE 12-Lipoxygenase extracellular vesicles colorectal cancer plasma membrane phospholipids |
| title | Platelets induce free and phospholipid-esterified 12-hydroxyeicosatetraenoic acid generation in colon cancer cells by delivering 12-lipoxygenase |
| title_full | Platelets induce free and phospholipid-esterified 12-hydroxyeicosatetraenoic acid generation in colon cancer cells by delivering 12-lipoxygenase |
| title_fullStr | Platelets induce free and phospholipid-esterified 12-hydroxyeicosatetraenoic acid generation in colon cancer cells by delivering 12-lipoxygenase |
| title_full_unstemmed | Platelets induce free and phospholipid-esterified 12-hydroxyeicosatetraenoic acid generation in colon cancer cells by delivering 12-lipoxygenase |
| title_short | Platelets induce free and phospholipid-esterified 12-hydroxyeicosatetraenoic acid generation in colon cancer cells by delivering 12-lipoxygenase |
| title_sort | platelets induce free and phospholipid esterified 12 hydroxyeicosatetraenoic acid generation in colon cancer cells by delivering 12 lipoxygenase |
| topic | blood platelets 12-HETE 12-Lipoxygenase extracellular vesicles colorectal cancer plasma membrane phospholipids |
| url | http://www.sciencedirect.com/science/article/pii/S0022227521000912 |
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