ArticleBreast cancer research : BCR2021
Attenuated TGFB signalling in macrophages decreases susceptibility to DMBA-induced mammary cancer in mice.
Article in Breast cancer research : BCR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 32 citations in OpenAlex.
- Multi-omic analysis of the liver-breast axis reveals key hepatic mediators of breast cancer progression.Science China. Life sciences · 2026Review
- Bioinformatic Approach to Identify Positive PrognosticInternational journal of molecular sciences · 2025Article
- Epithelial-Immune-Stromal Interactions Define Divergent Repair and Fibrosis Pathways After Acute Kidney Injury in Human Renal Transplants.bioRxiv : the preprint server for biology · 2025Article
- Marine derived macrolide bryostatin 4 inhibits the TGF-β signaling pathway against acute erythroleukemia.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Advancing osteoarthritis therapy with GMOCS hydrogel-loaded BMSCs-exos.Journal of nanobiotechnology · 2024Article
- Article
- TGFβ control of immune responses in cancer: a holistic immuno-oncology perspective.Nature reviews. Immunology · 2023Review
- CCL2-Mediated Stromal Interactions Drive Macrophage Polarization to Increase Breast Tumorigenesis.International journal of molecular sciences · 2023Article
- The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies.International journal of molecular sciences · 2023Review
- Article
- A role for platelets in metabolic reprogramming of tumor-associated macrophages.Frontiers in physiology · 2023Review
- Dynamic polarization of tumor-associated macrophages and their interaction with intratumoral T cells in an inflamed tumor microenvironment: from mechanistic insights to therapeutic opportunities.Frontiers in immunology · 2023Review
- Obesity contributes to hepatocellular carcinoma development via immunosuppressive microenvironment remodeling.Frontiers in immunology · 2023Review
- Estrogen-induced immune changes within the normal mammary gland.Scientific reports · 2022Article
- Biological Mechanisms and Therapeutic Opportunities in Mammographic Density and Breast Cancer Risk.Cancers · 2021Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundTransforming growth factor beta1 (TGFB1) is a multi-functional cytokine that regulates mammary gland development and cancer progression through endocrine, paracrine and autocrine mechanisms. TGFB1 also plays roles in tumour development and progression, and its increased expression is associated with an increased breast cancer risk. Macrophages are key target cells for TGFB1 action, also playing crucial roles in tumourigenesis. However, the precise role of TGFB-regulated macrophages in the mammary gland is unclear. This study investigated the effect of attenuated TGFB signalling in macrophages on mammary gland development and mammary cancer susceptibility in mice.
methodsA transgenic mouse model was generated, wherein a dominant negative TGFB receptor is activated in macrophages, in turn attenuating the TGFB signalling pathway specifically in the macrophage population. The mammary glands were assessed for morphological changes through wholemount and H&E analysis, and the abundance and phenotype of macrophages were analysed through immunohistochemistry. Another cohort of mice received carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), and tumour development was monitored weekly. Human non-neoplastic breast tissue was also immunohistochemically assessed for latent TGFB1 and macrophage marker CD68.
resultsAttenuation of TGFB signalling resulted in an increase in the percentage of alveolar epithelium in the mammary gland at dioestrus and an increase in macrophage abundance. The phenotype of macrophages was also altered, with inflammatory macrophage markers iNOS and CCR7 increased by 110% and 40%, respectively. A significant decrease in DMBA-induced mammary tumour incidence and prolonged tumour-free survival in mice with attenuated TGFB signalling were observed. In human non-neoplastic breast tissue, there was a significant inverse relationship between latent TGFB1 protein and CD68-positive macrophages.
conclusionsTGFB acts on macrophage populations in the mammary gland to reduce their abundance and dampen the inflammatory phenotype. TGFB signalling in macrophages increases mammary cancer susceptibility potentially through suppression of immune surveillance activities of macrophages.
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