ArticlePloS one2014
MDSCs mediate angiogenesis and predispose canine mammary tumor cells for metastasis via IL-28/IL-28RA (IFN-λ) signaling.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 70 citations in OpenAlex.
- Experimental models in immuno-oncology and their translational impact.Discover oncology · 2026Review
- A Literature Review of Interleukins in the Development and Treatment of Breast Cancer.International journal of molecular sciences · 2026Review
- The Promoting Angiogenesis and Its Clinical Significance of CD33Chronic diseases and translational medicine · 2026Article
- Expression of Interleukin 23 and Interleukin 28 in Mucinous & Non-Mucinous Colorectal Carcinoma and Their Relation to Clinicopathological Features and Prognosis.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Breast neoplasm epithelial-mesenchymal transition and cytokines: a systematic review.Cancer cell international · 2025Review
- IL-28A/IL-10Rβ axis promotes angiogenesis via eNOS/AKT signaling and AP-1/NF-κB/MMP-2 network by regulating HSP70-1 expression.Journal of advanced research · 2025Article
- TLR3 activation mediates partial epithelial-to-mesenchymal transition in human keratinocytes.Life science alliance · 2024Article
- Navigating tumor angiogenesis: therapeutic perspectives and myeloid cell regulation mechanism.Angiogenesis · 2024Review
- Dual roles of myeloid-derived suppressor cells in various diseases: a review.Archives of pharmacal research · 2024Review
- New treatment alternatives for primary and metastatic colorectal cancer by an integrated transcriptome and network analyses.Scientific reports · 2024Article
- Portraying the dark side of endogenous IFN-λ for promoting cancer progression and immunoevasion in pan-cancer.Journal of translational medicine · 2023Review
- Remodeling the tumor immune microenvironment via siRNA therapy for precision cancer treatment.Asian journal of pharmaceutical sciences · 2023Review
- MDSCs in breast cancer: an important enabler of tumor progression and an emerging therapeutic target.Frontiers in immunology · 2023Review
- Regulation of epithelial-mesenchymal transition by tumor microenvironmental signals and its implication in cancer therapeutics.Seminars in cancer biology · 2023Review
- Blood biomarkers for canine cancer, from human to veterinary oncology.Veterinary and comparative oncology · 2022Review
- Critical role of interferons in gastrointestinal injury repair.Nature communications · 2021Article
- Article
- Myeloid-derived suppressor cells in gastrointestinal cancers: A systemic review.World journal of gastrointestinal oncology · 2021Review
- Interferons in cancer immunoediting: sculpting metastasis and immunotherapy response.The Journal of clinical investigation · 2021Review
- Companion canines: an under-utilised model to aid in translating anti-metastatics to the clinic.Clinical & experimental metastasis · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMyeloid-derived suppressor cells (MDSCs) function in immunosuppression and tumor development by induction of angiogenesis in a STAT3-dependent manner. Knowledge of MDSC biology is mainly limited to mice studies, and more clinical investigations using spontaneous tumor models are required. Here we performed in vitro experiments and clinical data analysis obtained from canine patients.
methodsUsing microarrays we examined changes in gene expression in canine mammary cancer cells due to their co-culture with MDSCs. Further, using Real-time rt-PCR, Western blot, IHC, siRNA, angiogenesis assay and migration/invasion tests we examined a role of the most important signaling pathway.
resultsIn dogs with mammary cancer, the number of circulating MDSCs increases with tumor clinical stage. Microarray analysis revealed that MDSCs had significantly altered molecular pathways in tumor cells in vitro. Particularly important was the detected increased activation of IL-28/IL-28RA (IFN-λ) signaling. The highest expression of IL-28 was observed in stage III/IV mammary tumor-bearing dogs. IL-28 secreted by MDSCs stimulates STAT3 in tumor cells, which results in increased expression of angiogenic factors and subsequent induction of angiogenesis by endothelial cells, epithelial-mesenchymal transition (EMT) and increased migration of tumor cells in vitro. Knockdown of IL-28RA decreased angiogenesis, tumor cell invasion and migration.
conclusionsWe showed for the first time that MDSCs secrete IL-28 (IFN-λ), which promotes angiogenesis, EMT, invasion and migration of tumor cells. Thus, IL-28 may constitute an interesting target for further therapies. Moreover, the similarity in circulating MDSC levels at various tumor clinical stages between canine and human patients indicates canines as a good model for clinical trials of drugs targeting MDSCs.
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