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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/214406
Compartmentalized role of xCT in supporting pancreatic tumor growth, inflammation and mood disturbance in mice
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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.
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LARA, Olaya, JANSSEN, Pauline, MAMBRETTI, Marco, DE PAUW, Laura, ATES, Gamze, MACKENS, Liselotte, DE MUNCK, Jolien, WALCKIERS, Jarne, PAN, Zhaolong, BECKERS, Pauline, ESPINET, Elisa, SATO, Hideyo, DE RIDDER, Mark, MARKS, Daniel l., BARBÉ, Kurt, AERTS, Joeri l., HERMANS, Emmanuel, ROOMAN, Ilse, MASSIE, Ann. Compartmentalized role of xCT in supporting pancreatic tumor growth, inflammation and mood disturbance in mice. _Brain_. Behavior. Vol. and Immunity, núm. 2024, pàgs. 118. [consulta: 20 de gener de 2026]. ISSN: 1090-2139. [Disponible a: https://hdl.handle.net/2445/214406]