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Title:
Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein | Journal of Hematology & Oncology
Description:
Background The macrophage, one of the several key immune cell types, is believed to be involved in tumorigenesis. However, the mechanism of macrophages promoting tumor progression is largely unknown. Methods The differentially secreted proteins of M1 and M2 macrophages were analyzed by mass spectrometry. We performed GST pull-down assay for the identification of cell-membrane receptors that interact with chitinase 3-like protein 1 (CHI3L1) protein. The mouse model was used to validate the function of CHI3L1 in cancer metastasis in vivo. Protein phosphorylation and gene expression were performed to study the signaling pathway activation of cancer cells after CHI3L1 treatment. Results M2 macrophage-secreted CHI3L1 promoted the metastasis of gastric and breast cancer cells in vitro and in vivo. The CHI3L1 protein functioned by interacting with interleukin-13 receptor α2 chain (IL-13Rα2) molecules on the plasma membranes of cancer cells. Activation of IL-13Rα2 by CHI3L1 triggered the activation of the mitogen-activated protein kinase signaling pathway, leading to the upregulated expression of matrix metalloproteinase genes, which promoted tumor metastasis. The results of this study indicated that the level of CHI3L1 protein in the sera of patients with gastric or breast cancer was significantly elevated compared with those of healthy donors. Conclusions Our study revealed a novel aspect of macrophages with respect to cancer metastasis and showed that CHI3L1 could be a marker of metastatic gastric and breast cancer in patients.
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Keywords {š}
cancer, cells, chil, cell, macrophages, protein, breast, metastasis, gastric, mdamb, fig, article, pubmed, tumor, expression, google, scholar, cas, migration, invasion, ilrα, proteins, data, levels, isolated, results, adhesion, mice, mkn, showed, gene, signaling, patients, role, scalebar, ags, central, pathway, significantly, blood, antichil, macrophage, culture, rchil, promote, study, compared, recombinant, cocultured, assays,
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tgf-β-induced epithelial-mesenchymal transition ras/raf-1/erk/ap-1 signaling pathway granulocyte-macrophage colony-stimulating factor c-jun n-terminal kinase erk-nf-κb signaling full size image selective jnk/ap-1/mmp-2 modulation article download pdf m2 macrophage-derived chi3l1 chi3l1-mediated il-13rα2 activation mitogen-activated protein kinase exclusively tam-derived cytokines suppress t-cell proliferation promote solid-tumor metastasis dual-luciferase reporter assays quantitative real-time pcr erα-negative breast cancer pro-inflammatory cytokines derived human leukocyte antigen-drα t-cell stimulatory cytokines peripheral blood monocytes mediate cell-cell interactions m2-secreted oncogenic protein il-13rα2 receptor activated perform anti-tumor functions il-13rα2-sirna transfection western blotting-based determination il-13rα2 gene silencing il-13rα2 gene expression tumor-derived signals macrophage-mediated mechanism chi3l1-ap-1-mmp pathway sds-page denaturing gel polyclonal anti-chi3l1 antibody mda-mb-435 cell metastasis mda-mb-231 cell metastasis myeloid wnt7b mediates m2 macrophage secretions pi3k/akt signaling pathways c-jun protein expression fluorescently labeled anti-chi3l1 m2 macrophages derived full access chi3l1-binding membrane receptor c-jun expression levels published article chi3l1-il-13rα2 interaction colony-stimulating factor-1 hla-drα-positive macrophages monocyte-derived m1
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headline:Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein
description:The macrophage, one of the several key immune cell types, is believed to be involved in tumorigenesis. However, the mechanism of macrophages promoting tumor progression is largely unknown. The differentially secreted proteins of M1 and M2 macrophages were analyzed by mass spectrometry. We performed GST pull-down assay for the identification of cell-membrane receptors that interact with chitinase 3-like protein 1 (CHI3L1) protein. The mouse model was used to validate the function of CHI3L1 in cancer metastasis in vivo. Protein phosphorylation and gene expression were performed to study the signaling pathway activation of cancer cells after CHI3L1 treatment. M2 macrophage-secreted CHI3L1 promoted the metastasis of gastric and breast cancer cells in vitro and in vivo. The CHI3L1 protein functioned by interacting with interleukin-13 receptor α2 chain (IL-13Rα2) molecules on the plasma membranes of cancer cells. Activation of IL-13Rα2 by CHI3L1 triggered the activation of the mitogen-activated protein kinase signaling pathway, leading to the upregulated expression of matrix metalloproteinase genes, which promoted tumor metastasis. The results of this study indicated that the level of CHI3L1 protein in the sera of patients with gastric or breast cancer was significantly elevated compared with those of healthy donors. Our study revealed a novel aspect of macrophages with respect to cancer metastasis and showed that CHI3L1 could be a marker of metastatic gastric and breast cancer in patients.
datePublished:2017-02-01T00:00:00Z
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headline:Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein
description:The macrophage, one of the several key immune cell types, is believed to be involved in tumorigenesis. However, the mechanism of macrophages promoting tumor progression is largely unknown. The differentially secreted proteins of M1 and M2 macrophages were analyzed by mass spectrometry. We performed GST pull-down assay for the identification of cell-membrane receptors that interact with chitinase 3-like protein 1 (CHI3L1) protein. The mouse model was used to validate the function of CHI3L1 in cancer metastasis in vivo. Protein phosphorylation and gene expression were performed to study the signaling pathway activation of cancer cells after CHI3L1 treatment. M2 macrophage-secreted CHI3L1 promoted the metastasis of gastric and breast cancer cells in vitro and in vivo. The CHI3L1 protein functioned by interacting with interleukin-13 receptor α2 chain (IL-13Rα2) molecules on the plasma membranes of cancer cells. Activation of IL-13Rα2 by CHI3L1 triggered the activation of the mitogen-activated protein kinase signaling pathway, leading to the upregulated expression of matrix metalloproteinase genes, which promoted tumor metastasis. The results of this study indicated that the level of CHI3L1 protein in the sera of patients with gastric or breast cancer was significantly elevated compared with those of healthy donors. Our study revealed a novel aspect of macrophages with respect to cancer metastasis and showed that CHI3L1 could be a marker of metastatic gastric and breast cancer in patients.
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CHI3L1
IL-13Rα2
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Oncology
Hematology
Cancer Research
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