ArticleBMC cancer2014
Tumor-associated macrophage-derived IL-6 and IL-8 enhance invasive activity of LoVo cells induced by PRL-3 in a KCNN4 channel-dependent manner.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- Modulation of tumor-associated macrophage activity with radiation therapy: a systematic review.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023Pooled it
- Whole blood expression profiling from the TREAT trial: insights for the pathogenesis of polyarticular juvenile idiopathic arthritis.Arthritis research & therapy · 2016Trial
- Prognostic Impact of IL6 Genetic Variants in Patients with Metastatic Colorectal Cancer Treated with Bevacizumab-Based Chemotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- Potassium channels in cancer: from hallmarks to therapeutic targeting.Journal of physiology and biochemistry · 2026Review
- NLRC5-Deficient Macrophages Promote a Tumor-Permissive Phenotype via AXL- and MERTK-Mediated Efferocytosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Review
- Modulatory Effects of Bioactive Phytoconstituents on the Amplitude and Gating Properties of Membrane Ion Channels.Molecules (Basel, Switzerland) · 2026Review
- PRL-3 up-regulates exosomal ITGαvβ5 expression to promote liver pre-metastatic niche formation and colon cancer liver metastasis.Experimental hematology & oncology · 2026Article
- PRL-3 as a metastasis-associated phosphatase in colorectal cancer: Mechanisms and therapeutic strategies.Clinical & experimental metastasis · 2025Review
- Emerging Strategies for Targeting Angiogenesis and the Tumor Microenvironment in Gastrointestinal Malignancies: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Pilot Study of Intratumoral Immunotherapy with Cowpea Mosaic Virus Nanoparticles: Safety in Refractory Canine Oral Tumors.Molecular pharmaceutics · 2025Article
- Article
- Interleukin-6 as a Predictive Marker for Lymph Node and Distant Metastasis in Colorectal Cancer: A Retrospective Cohort Study.Cancer management and research · 2025Article
- The role of macrophages in liver metastasis: mechanisms and therapeutic prospects.Frontiers in immunology · 2025Review
- IDH2 regulates macrophage polarization and tumorigenesis by modulating mitochondrial metabolism in macrophages.Molecular medicine (Cambridge, Mass.) · 2024Article
- Adipocyte pyroptosis occurs in omental tumor microenvironment and is associated with chemoresistance of ovarian cancer.Journal of biomedical science · 2024Article
- Glutamine-derived aspartate is required for eIF5A hypusination-mediated translation of HIF-1α to induce the polarization of tumor-associated macrophages.Experimental & molecular medicine · 2024Article
- M2 macrophage‑derived exosomes alleviate KCa3.1 channel expression in rapidly paced HL‑1 myocytes via the NF‑κB (p65)/STAT3 signaling pathway.Molecular medicine reports · 2024Article
- Challenges in the Therapeutic Targeting of KCa Channels: From Basic Physiology to Clinical Applications.International journal of molecular sciences · 2024Review
- Tumor-associated macrophages in colorectal cancer metastasis: molecular insights and translational perspectives.Journal of translational medicine · 2024Review
15 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor-associated macrophages (TAMs) are known to promote cancer progression and metastasis through the release of a variety of cytokines. Phosphatase of regenerating liver (PRL-3) has been considered as a marker of colorectal cancer (CRC) liver metastasis. Our previous research suggests that PRL-3 can enhance the metastasis of CRC through the up-regulation of intermediate-conductance Ca2+-activated K+ (KCNN4) channel, which is dependent on the autocrine secretion of tumor necrosis factor-alpha (TNF-α). However, whether TAMs participate in the progression and metastasis of CRC induced by PRL-3 remains unknown.
methodsWe used flow cytometry, coculture, western blotting, invasion assays, real-time quantitative PCR, chromatin immunoprecipitation, luciferase reporter assays, and immunofluorescence staining to determine the effect of TAMs on the ability of PRL-3 to promote invasiveness of CRC cells.
resultsIn this study, we found that TAMs facilitated the metastasis of CRC induced by PRL-3. When TAMs were cocultured with CRC cells, the expression of KCNN4 was increased in TAMs and the invasion of CRC cells was enhanced. Furthermore, cytokines that were secreted by TAMs, such as IL-6 and IL-8, were also significantly increased. This response was attenuated by treating TAMs with the KCNN4 channel-specific inhibitor, 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34), which suggested that KCNN4 channels may be involved in inducing the secretion of IL-6 and IL-8 by TAMs and improving CRC cell invasiveness. Moreover, the expression of KCNN4 channels in TAMs was regulated through the NF-κB signal pathway, which is activated by TNF-α from CRC cells. Immunofluorescence analysis of colorectal specimens indicated that IL-6 and IL-8 double positive cells in the stroma showed positive staining for the TAM marker CD68, suggesting that TAMs produce IL-6 and IL-8. Increased numbers of these cells correlated with higher clinical stage.
conclusionsOur findings suggested that TAMs participate in the metastasis of CRC induced by PRL-3 through the TNF-α mediated secretion of IL-6 and IL-8 in a paracrine manner.
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