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http://hdl.handle.net/2445/214406
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DC Field | Value | Language |
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dc.contributor.author | Lara, Olaya | - |
dc.contributor.author | Janssen, Pauline | - |
dc.contributor.author | Mambretti, Marco | - |
dc.contributor.author | De Pauw, Laura | - |
dc.contributor.author | Ates, Gamze | - |
dc.contributor.author | Mackens, Liselotte | - |
dc.contributor.author | De Munck, Jolien | - |
dc.contributor.author | Walckiers, Jarne | - |
dc.contributor.author | Pan, Zhaolong | - |
dc.contributor.author | Beckers, Pauline | - |
dc.contributor.author | Espinet, Elisa | - |
dc.contributor.author | Sato, Hideyo | - |
dc.contributor.author | De Ridder, Mark | - |
dc.contributor.author | Marks, Daniel L. | - |
dc.contributor.author | Barbé, Kurt | - |
dc.contributor.author | Aerts, Joeri L. | - |
dc.contributor.author | Hermans, Emmanuel | - |
dc.contributor.author | Rooman, Ilse | - |
dc.contributor.author | Massie, Ann | - |
dc.date.accessioned | 2024-07-05T11:53:51Z | - |
dc.date.available | 2024-07-05T11:53:51Z | - |
dc.date.issued | 2024-05-01 | - |
dc.identifier.uri | http://hdl.handle.net/2445/214406 | - |
dc.description.abstract | xCT (Slc7a11), the specific subunit of the cystine/glutamate antiporter system x c - , is present in the brain and on immune cells, where it is known to modulate behavior and inflammatory responses. In a variety of cancers -including pancreatic ductal adenocarcinoma (PDAC)-, xCT is upregulated by tumor cells to support their growth and spread. Therefore, we studied the impact of xCT deletion in pancreatic tumor cells (Panc02) and/or the host (xCT -/- mice) on tumor burden, inflammation, cachexia and mood disturbances. Deletion of xCT in the tumor strongly reduced tumor growth. Targeting xCT in the host and not the tumor resulted only in a partial reduction of tumor burden, while it did attenuate tumor -related systemic inflammation and prevented an increase in immunosuppressive regulatory T cells. The latter effect could be replicated by specific xCT deletion in immune cells. xCT deletion in the host or the tumor differentially modulated neuroinflammation. When mice were grafted with xCT-deleted tumor cells, hypothalamic inflammation was reduced and, accordingly, food intake improved. Tumor bearing xCT -/- mice showed a trend of reduced hippocampal neuroinflammation with less anxiety- and depressive -like behavior. Taken together, targeting xCT may have beneficial effects on pancreatic cancer -related comorbidities, beyond reducing tumor burden. The search for novel and specific xCT inhibitors is warranted as they may represent a holistic therapy in pancreatic cancer. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Elsevier BV | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1016/j.bbi.2024.03.001 | - |
dc.relation.ispartof | Brain, Behavior, and Immunity, 2024, vol. 118, p. 275-286 | - |
dc.relation.uri | https://doi.org/10.1016/j.bbi.2024.03.001 | - |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.title | Compartmentalized role of xCT in supporting pancreatic tumor growth, inflammation and mood disturbance in mice | - |
dc.type | info:eu-repo/semantics/article | - |
dc.date.updated | 2024-06-20T12:16:58Z | - |
dc.rights.accessRights | info:eu-repo/semantics/embargoedAccess | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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1-s2.0-S0889159124002812-main.pdf | 1.73 MB | Adobe PDF | View/Open |
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