Death Receptor 5 Displayed on Extracellular Vesicles Decreases TRAIL Sensitivity of Colon Cancer Cells
Tumor necrosis factor–related apoptosis inducing ligand (TRAIL) is considered to be a promising antitumor drug because of its selective proapoptotic properties on tumor cells. However, the clinical application of TRAIL is until now limited because of the resistance of several cancer cells, which can...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00318/full |
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| author | Rita Setroikromo Baojie Zhang Carlos R. Reis Rima H. Mistry Wim J. Quax |
| author_facet | Rita Setroikromo Baojie Zhang Carlos R. Reis Rima H. Mistry Wim J. Quax |
| author_sort | Rita Setroikromo |
| collection | DOAJ |
| description | Tumor necrosis factor–related apoptosis inducing ligand (TRAIL) is considered to be a promising antitumor drug because of its selective proapoptotic properties on tumor cells. However, the clinical application of TRAIL is until now limited because of the resistance of several cancer cells, which can occur at various levels in the TRAIL signaling pathway. The role of decoy receptors that can side-track TRAIL, thereby preventing the formation of an activated death receptor, has been extensively studied. In this study, we have focused on extracellular vesicles (EVs) that are known to play a role in cell-to-cell communication and that can be released by donor cells into the medium transferring their components to recipient cells. TRAIL-induced apoptotic signaling is triggered upon the binding of two death receptors, DR4 and DR5. Here, we found that DR5 but not DR4 is present in the conditioned medium (CM)–derived from various cancer cells. Moreover, we observed that DR5 was exposed on EVs and can act as “decoy receptor” for binding to TRAIL. This results in a strongly reduced number of apoptotic cells upon treatment with DR5-specific TRAIL variant DHER in CM. This reduction happened with EVs containing either the long or short isoform of DR5. Taken together, we demonstrated that colon rectal tumor cells can secrete DR5-coated EVs, and this can cause TRAIL resistance. This is to our knowledge a novel finding and provides new insights into understanding TRAIL sensitivity. |
| first_indexed | 2024-12-13T09:16:16Z |
| format | Article |
| id | doaj.art-97c0f6c280154b58be4462dff5229991 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-13T09:16:16Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-97c0f6c280154b58be4462dff52299912022-12-21T23:52:50ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-05-01810.3389/fcell.2020.00318529436Death Receptor 5 Displayed on Extracellular Vesicles Decreases TRAIL Sensitivity of Colon Cancer CellsRita SetroikromoBaojie ZhangCarlos R. ReisRima H. MistryWim J. QuaxTumor necrosis factor–related apoptosis inducing ligand (TRAIL) is considered to be a promising antitumor drug because of its selective proapoptotic properties on tumor cells. However, the clinical application of TRAIL is until now limited because of the resistance of several cancer cells, which can occur at various levels in the TRAIL signaling pathway. The role of decoy receptors that can side-track TRAIL, thereby preventing the formation of an activated death receptor, has been extensively studied. In this study, we have focused on extracellular vesicles (EVs) that are known to play a role in cell-to-cell communication and that can be released by donor cells into the medium transferring their components to recipient cells. TRAIL-induced apoptotic signaling is triggered upon the binding of two death receptors, DR4 and DR5. Here, we found that DR5 but not DR4 is present in the conditioned medium (CM)–derived from various cancer cells. Moreover, we observed that DR5 was exposed on EVs and can act as “decoy receptor” for binding to TRAIL. This results in a strongly reduced number of apoptotic cells upon treatment with DR5-specific TRAIL variant DHER in CM. This reduction happened with EVs containing either the long or short isoform of DR5. Taken together, we demonstrated that colon rectal tumor cells can secrete DR5-coated EVs, and this can cause TRAIL resistance. This is to our knowledge a novel finding and provides new insights into understanding TRAIL sensitivity.https://www.frontiersin.org/article/10.3389/fcell.2020.00318/fullextracellular vesiclesDR5TRAILapoptosisconditioned mediumreceptor–ligand trafficking |
| spellingShingle | Rita Setroikromo Baojie Zhang Carlos R. Reis Rima H. Mistry Wim J. Quax Death Receptor 5 Displayed on Extracellular Vesicles Decreases TRAIL Sensitivity of Colon Cancer Cells Frontiers in Cell and Developmental Biology extracellular vesicles DR5 TRAIL apoptosis conditioned medium receptor–ligand trafficking |
| title | Death Receptor 5 Displayed on Extracellular Vesicles Decreases TRAIL Sensitivity of Colon Cancer Cells |
| title_full | Death Receptor 5 Displayed on Extracellular Vesicles Decreases TRAIL Sensitivity of Colon Cancer Cells |
| title_fullStr | Death Receptor 5 Displayed on Extracellular Vesicles Decreases TRAIL Sensitivity of Colon Cancer Cells |
| title_full_unstemmed | Death Receptor 5 Displayed on Extracellular Vesicles Decreases TRAIL Sensitivity of Colon Cancer Cells |
| title_short | Death Receptor 5 Displayed on Extracellular Vesicles Decreases TRAIL Sensitivity of Colon Cancer Cells |
| title_sort | death receptor 5 displayed on extracellular vesicles decreases trail sensitivity of colon cancer cells |
| topic | extracellular vesicles DR5 TRAIL apoptosis conditioned medium receptor–ligand trafficking |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00318/full |
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