ArticlePloS one2014
Progastrin represses the alternative activation of human macrophages and modulates their influence on colon cancer epithelial cells.
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 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Distribution and prognostic value of macrophages in colorectal cancer and adjacent mucosa in patient stages I-IIIWorld journal of gastroenterology · 2026Article
- Progastrin, annexin A2, and tumor-associated macrophages in gastric adenocarcinoma.Journal of pathology and translational medicine · 2026Article
- MiR-548t-5p regulates pancreatic ductal adenocarcinoma metastasis through an IL-33-dependent crosstalk between cancer cells and M2 macrophages.Cell cycle (Georgetown, Tex.) · 2024Article
- Two tripartite classification systems of CD86Frontiers in immunology · 2023Article
- Review
- The Ratio of CD86+/CD163+ Macrophages Predicts Postoperative Recurrence in Stage II-III Colorectal Cancer.Frontiers in immunology · 2021Article
- The FBW7-MCL-1 axis is key in M1 and M2 macrophage-related colon cancer cell progression: validating the immunotherapeutic value of targeting PI3Kγ.Experimental & molecular medicine · 2020Article
- CD86PeerJ · 2020Article
- Macrophages as an Emerging Source of Wnt Ligands: Relevance in Mucosal Integrity.Frontiers in immunology · 2019Review
- Characteristics and potential role of M2 macrophages in COPD.International journal of chronic obstructive pulmonary disease · 2017Article
- Gastrin attenuates ischemia-reperfusion-induced intestinal injury in rats.Experimental biology and medicine (Maywood, N.J.) · 2016Article
- CD86⁺/CD206⁺, Diametrically Polarized Tumor-Associated Macrophages, Predict Hepatocellular Carcinoma Patient Prognosis.International journal of molecular sciences · 2016Article
- Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophage infiltration is a negative prognostic factor for most cancers but gastrointestinal tumors seem to be an exception. The effect of macrophages on cancer progression depends on their phenotype, which may vary between M1 (pro-inflammatory, defensive) to M2 (tolerogenic, pro-tumoral). Gastrointestinal cancers often become an ectopic source of gastrins and macrophages present receptors for these peptides. The aim of the present study is to analyze whether gastrins can affect the pattern of macrophage infiltration in colorectal tumors. We have evaluated the relationship between gastrin expression and the pattern of macrophage infiltration in samples from colorectal cancer and the influence of these peptides on the phenotype of macrophages differentiated from human peripheral monocytes in vitro. The total number of macrophages (CD68+ cells) was similar in tumoral and normal surrounding tissue, but the number of M2 macrophages (CD206+ cells) was significantly higher in the tumor. However, the number of these tumor-associated M2 macrophages correlated negatively with the immunoreactivity for gastrin peptides in tumor epithelial cells. Macrophages differentiated from human peripheral monocytes in the presence of progastrin showed lower levels of M2-markers (CD206, IL10) with normal amounts of M1-markers (CD86, IL12). Progastrin induced similar effects in mature macrophages treated with IL4 to obtain a M2-phenotype or with LPS plus IFNγ to generate M1-macrophages. Macrophages differentiated in the presence of progastrin presented a reduced expression of Wnt ligands and decreased the number and increased cell death of co-cultured colorectal cancer epithelial cells. Our results suggest that progastrin inhibits the acquisition of a M2-phenotype in human macrophages. This effect exerted on tumor associated macrophages may modulate cancer progression and should be taken into account when analyzing the therapeutic value of gastrin immunoneutralization.
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