ArticlePloS one2021
Adenosine/TGFβ axis in regulation of mammary fibroblast functions.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
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- Evaluation of CNPase and TGFβ1/Smad Signalling Pathway Molecule Expression in Sinus Epithelial Tissues of Patients with Chronic Rhinosinusitis with (CRSwNP) and without Nasal Polyps (CRSsNP).Journal of personalized medicine · 2024Article
- Cordycepin Triphosphate as a Potential Modulator of Cellular Plasticity in Cancer via cAMP-Dependent Pathways: An In Silico Approach.International journal of molecular sciences · 2024Article
- Selective refueling of CAR T cells using ADA1 and CD26 boosts antitumor immunity.Cell reports. Medicine · 2024Article
- Cross-Talk between the TGF-β and Cell Adhesion Signaling Pathways in Cancer.International journal of medical sciences · 2024Review
- A2B Adenosine Receptor in Idiopathic Pulmonary Fibrosis: Pursuing Proper Pit Stop to Interfere with Disease Progression.International journal of molecular sciences · 2023Review
- Ecto-5'-nucleotidase (Nt5e/CD73)-mediated adenosine signaling attenuates TGFβ-2 induced elastin and cellular contraction.American journal of physiology. Cell physiology · 2023Article
- Biglycan Involvement in Heart Fibrosis: Modulation of Adenosine 2A Receptor Improves Damage in Immortalized Cardiac Fibroblasts.International journal of molecular sciences · 2023Article
- Article
- Adenosine Receptor A2B Negatively Regulates Cell Migration in Ovarian Carcinoma Cells.International journal of molecular sciences · 2022Article
- Current Adenosinergic Therapies: What Do Cancer Cells Stand to Gain and Lose?International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Cancer associated fibroblasts (CAF) play a key role in cancer progression and metastasis. Diminished TGFβ response on CAF correlates with poor outcome and recurrence in cancer patients. Mechanisms behind lost TGFβ signaling on CAF are poorly understood, but, utilizing MMTV-PyMT mouse model, we have previously demonstrated that in tumor microenvironment myeloid cells, producing adenosine, contribute to downregulated TGFβ signaling on CAFs. In the current work, we performed serial in vitro studies to investigate the role of adenosine/TGFβ axis in mouse mammary fibroblast functions, i.e., proliferation, protein expression, migration, and contractility. We found that adenosine analog NECA diminished TGFβ-induced CCL5 and MMP9 expression. Additionally, we discovered that NECA completely inhibited effect of TGFβ to upregulate αSMA, key protein of cytoskeletal rearrangements, necessary for migration and contractility of fibroblasts. Our results show that TGFβ increases contractility of mouse mammary fibroblasts and human fibroblast cell lines, and NECA attenuates theses effects. Using pharmacological approach and genetically modified animals, we determined that NECA effects on TGFβ pathway occur via A2A/A2B adenosine receptor-AC-PKA dependent manner. Using isolated CD11b+ cells from tumor tissue of CD73-KO and CD39-KO animals in co-culture experiments with ATP and AMP, we confirmed that myeloid cells can affect functions of mammary fibroblasts through adenosine signaling. Our data suggest a novel mechanism of interaction between adenosine and TGFβ signaling pathways that can impact phenotype of fibroblasts in a tumor microenvironment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.