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Please use this identifier to cite or link to this item: 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, et al. Compartmentalized role of xCT in supporting pancreatic tumor growth, inflammation and mood disturbance in mice. Brain. Behavior. Vol. and Immunity, num. 2024, pags. 118. ISSN 1090-2139. [consulted: 8 of June of 2026]. Available at: https://hdl.handle.net/2445/214406