ArticleBreast cancer research : BCR2014
Cancer/stroma interplay via cyclooxygenase-2 and indoleamine 2,3-dioxygenase promotes breast cancer progression.
Article in Breast cancer research : BCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.
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- Targeting tryptophan metabolism in breast cancer immunotherapy: Recent advances and future prospects.Translational oncology · 2026Review
- Gut microbiota-regulated tryptophan metabolism in breast cancer: mechanisms and therapeutic perspectives.Frontiers in oncology · 2026Review
- Role of Tryptophan Metabolism in Cancer.Cancer innovation · 2025Review
- The aryl hydrocarbon receptor: a rehabilitated target for therapeutic immune modulation.Nature reviews. Drug discovery · 2025Review
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- Identification of Biomarkers Based on Starvation Response-Related Genes for Assessing the Immune Profile and Prognosis in Lung Adenocarcinoma.International journal of genomics · 2025Article
- Cannabidiol Suppresses Metastatic Castration-Resistant Prostate Cancer Progression and Recurrence through Modulating Tryptophan Catabolism.ACS pharmacology & translational science · 2024Article
- Distinct functions of wild-type and R273H mutant Δ133p53α differentially regulate glioblastoma aggressiveness and therapy-induced senescence.Cell death & disease · 2024Article
- Targeting aryl hydrocarbon receptor to prevent cancer in barrier organs.Biochemical pharmacology · 2024Review
- Article
- Metabolic Reprogramming of Cancer-Associated Fibroblast in the Tumor Microenvironment: From Basics to Clinic.Clinical Medicine Insights. Oncology · 2024Review
- Targeting amino acid-metabolizing enzymes for cancer immunotherapy.Frontiers in immunology · 2024Review
- Untargeted metabolomics yields insight into extramammary Paget's disease mechanisms.Frontiers in oncology · 2024Article
- Distinct functions of wild-type and R273H mutant Δ133p53α differentially regulate glioblastoma aggressiveness and therapy-induced senescence.Research square · 2023Article
- Immune Regulatory Function of Cancer- Associated Fibroblasts in Non-small Cell Lung Cancer.Tuberculosis and respiratory diseases · 2023Article
- The Role of Amino Acids in the Diagnosis, Risk Assessment, and Treatment of Breast Cancer: A Review.Current issues in molecular biology · 2023Review
- Involvement of the kynurenine pathway in breast cancer: updates on clinical research and trials.British journal of cancer · 2023Review
- Metabolic heterogeneity in early-stage lung adenocarcinoma revealed by RNA-seq and scRNA-seq.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- The Interplay between Microbiota and Chemotherapy-Derived Metabolites in Breast Cancer.Metabolites · 2023Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionExpression of indoleamine 2,3-dioxygenase (IDO) in primary breast cancer increases tumor growth and metastasis. However, the clinical significance of stromal IDO and the regulation of stromal IDO are unclear.
methodsMetabolomics and enzyme-linked immunosorbent assay (ELISA) were used to study the effect of cyclooxygenase-2 (COX-2)-overexpressing breast cancer cells on IDO expression in co-cultured human breast fibroblasts. Biochemical inhibitors and short-hairpin RNA (shRNA) were used to clarify how prostaglandin E2 (PGE2) upregulates IDO expression. Associations of stromal IDO with clinicopathologic parameters were tested in tumor specimens. An orthotopic animal model was used to examine the effect of COX-2 and IDO inhibitors on tumor growth.
resultsKynurenine, the metabolite generated by IDO, increases in the supernatant of fibroblasts co-cultured with COX-2-overexpressing breast cancer cells. PGE2 released by cancer cells upregulates IDO expression in fibroblasts through an EP4/signal transducer and activator of transcription 3 (STAT3)-dependent pathway. Conversely, fibroblast-secreted kynurenine promotes the formation of the E-cadherin/Aryl hydrocarbon receptor (AhR)/S-phase kinase-associated protein 2 (Skp2) complex, resulting in degradation of E-cadherin to increase breast cancer invasiveness. The enhancement of motility of breast cancer cells induced by co-culture with fibroblasts is suppressed by the IDO inhibitor 1-methyl-tryptophan. Pathological analysis demonstrates that upregulation of stromal IDO is a poor prognosis factor and is associated with of COX-2 overexpression. Co-expression of cancer COX-2 and stromal IDO predicts a worse disease-free and metastasis-free survival. Finally, COX-2 and IDO inhibitors inhibit tumor growth in vivo.
conclusionIntegration of metabolomics and molecular and pathological approaches reveals the interplay between cancer and stroma via COX-2, and IDO promotes tumor progression and predicts poor patient survival.
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