Tryptophan 2,3‐dioxygenase‐positive matrix fibroblasts fuel breast cancer lung metastasis via kynurenine‐mediated ferroptosis resistance of metastatic cells and T cell dysfunction

Cancer Communications, Journal Year: 2024, Volume and Issue: 44(11), P. 1261 - 1286

Published: Sept. 2, 2024

Abstract Background Tumor metastasis is a major threat to cancer patient survival. The organ‐specific niche plays pivotal role in tumor organotropic metastasis. Fibroblasts serve as vital component of the metastatic microenvironment, but how heterogeneous metastasis‐associated fibroblasts (MAFs) promote poorly characterized. Here, we aimed decipher heterogeneity MAFs and elucidate distinct roles these pulmonary formation breast cancer. Methods Mouse models were established using an vivo selection method repeated injections cells purified from mouse lung. Single‐cell RNA‐sequencing (scRNA‐seq) was employed investigate MAFs. Transgenic mice used examine contribution tryptophan 2,3‐dioxygenase‐positive matrix (TDO2 + MFs) lung Results We uncovered 3 subtypes their transcriptome profiles changed dynamically evolved. As predominant subtype, MFs exclusively marked by platelet‐derived growth factor receptor alpha (PDGFRA) mainly located on edge metastasis, T enriched around MFs. Notably, high MF signatures significantly associated with poor survival patients. Lung metastases markedly diminished, suppression dramatically attenuated MF‐depleted experimental models. found that TDO2 controlled producing kynurenine (KYN), which upregulated ferritin heavy chain 1 (FTH1) level disseminated (DTCs), enabling DTCs resist ferroptosis. Moreover, MF‐secreted chemokines C‐C motif chemokine ligand 8 (CCL8) 11 (CCL11) recruited cells. MF‐derived KYN induced cell dysfunction. Conditional knockout Tdo2 diminished enhanced immune activation. Conclusions Our study reveals crucial promoting DTCs’ evasion niche. It suggests targeting metabolism lung‐specific stromal may be effective treatment strategy for patients

Language: Английский

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TDO Target Inhibitor Research Progress Review

Journal of Biosciences and Medicines, Journal Year: 2025, Volume and Issue: 13(03), P. 356 - 368

Published: Jan. 1, 2025

Language: Английский

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Lymphangiogenesis in mouse embryonic and early postnatal ovaries

Gene Expression Patterns, Journal Year: 2025, Volume and Issue: unknown, P. 119393 - 119393

Published: April 1, 2025

Language: Английский

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Unraveling the breast cancer tumor microenvironment: crucial factors influencing natural killer cell function and therapeutic strategies

International Journal of Biological Sciences, Journal Year: 2025, Volume and Issue: 21(6), P. 2606 - 2628

Published: March 24, 2025

Natural killer (NK) cells have emerged as a novel and effective treatment for breast cancer. Nevertheless, the cancer tumor microenvironment (TME) manifests multiple immunosuppressive mechanisms, impeding proper execution of NK cell functions. This review summarizes recent research on influence TME functionality in It delves into effects internal environment elucidates roles diverse stromal components, immune cells, signaling molecules regulating activity within TME. also therapeutic strategies based small-molecule inhibitors, antibody therapies, natural products, well progress preclinical clinical trials. By enhancing our understanding formulating to counteract its effects, we could fully harness promise treatment.

Language: Английский

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New insights into tryptophan metabolism in cancer

Trends in cancer, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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