ArticleCancer biology & therapy2015
PTEN inhibits macrophage polarization from M1 to M2 through CCL2 and VEGF-A reduction and NHERF-1 synergism.
Article in Cancer biology & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Prognostic Significance of Tumor-Associated Macrophage Content in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis.Frontiers in oncology · 2019Pooled it
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- Identification of LILRB4 as a regulator of M2c macrophages and a potential immunotherapeutic target in ovarian cancer.Frontiers in immunology · 2026Article
- Plasma cell-CD8+ T cell co-enrichment distinguishes immunotherapy-responsive hepatocellular carcinoma subtypes.eGastroenterology · 2026Article
- Mechanism and role of regulated cell death in tumor immunity and immunotherapy.Cancer communications (London, England) · 2025Review
- Exosome, an important transmitter in the drug resistance of non-small cell lung cancer.Frontiers in oncology · 2025Review
- Preconditioning of Mesenchymal Stem Cells Enhances the Neuroprotective Effects of Their Conditioned Medium in an Alzheimer's Disease In Vitro Model.Biomedicines · 2024Article
- Pre-metastatic niche: formation, characteristics and therapeutic implication.Signal transduction and targeted therapy · 2024Review
- Non-apoptotic regulated cell death mediates reprogramming of the tumour immune microenvironment by macrophages.Journal of cellular and molecular medicine · 2024Review
- Decoding the Tumour Microenvironment: Molecular Players, Pathways, and Therapeutic Targets in Cancer Treatment.Cancers · 2024Review
- Gender Differences in a Mouse Model of Hepatocellular Carcinoma Revealed Using Multi-Modal Imaging.Cancers · 2023Article
- Inhibition of YAP1 activity ameliorates acute lung injury through promotion of M2 macrophage polarization.MedComm · 2023Article
- Anticancer effects and mechanisms of astragaloside‑IV (Review).Oncology reports · 2023Review
- Tumor-associated macrophages: an effective player of the tumor microenvironment.Frontiers in immunology · 2023Review
- Tumor-derived Cav-1 promotes pre-metastatic niche formation and lung metastasis in breast cancer.Theranostics · 2023Article
- Protein phosphatases regulate the liver microenvironment in the development of hepatocellular carcinoma.Experimental & molecular medicine · 2022Review
- Autophagy in Cancer Immunotherapy.Cells · 2022Review
- Macrophage Polarization and Reprogramming in Acute Inflammation: A Redox Perspective.Antioxidants (Basel, Switzerland) · 2022Review
- Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy.Signal transduction and targeted therapy · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PTEN has been studied in several tumor models as a tumor suppressor. In this study, we explored the role of PTEN in the inhibition state of polarized M2 subtype of macrophage in tumor microenvironment (TME) and the underlying mechanisms. To elucidate the potential effect in TME, RAW 264.7 macrophages and 4T1 mouse breast cancer cells were co-cultured to reconstruct tumor microenvironment. After PTEN was down-regulated with shRNA, the expression of CCL2 and VEGF-A, which are definited to promote the formation of M2 macrophages, have a dramatically increase on the level of both gene and protein in co-cultured RAW 264.7 macrophages. And at the same time, NHERF-1 (Na(+)/H(+) exchanger regulating factor-1), another tumor suppressor has a similar tendency to PTEN. Q-PCR and WB results suggested that PTEN and NHERF-1 were consistent with one another no matter at mRNA or protein level when exposed to the same stimulus. Coimmunoprecipitation and immunofluorescence techniques confirmed that PTEN and NHERF-1 were coprecipitated, and NHERF-1 protein expression was properly reduced with rCCL2 effect. In addition, cell immunofluorescence images revealed a profound transferance, in co-cultured RAW 264.7 macrophages, an up-regulation of NHERF-1 could promote the PTEN marked expression on the cell membrane, and this form for the interaction was not negligible. These observations illustrate PTEN with a certain synergy of NHERF-1, as well as down-regulation of CCL2 suppressing M2 macrophage transformation pathway. The results suggest that the activation of PTEN and NHERF-1 may impede the evolution of macrophages beyond the M1 into M2 phenotype in tumor microenvironment.
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