Using the MMTV-PyVmT/FVB mammary tumor model, we demonstrate a novel role for CCL2/CCR2 chemokine signaling in tumor progression by altering the microenvironment.
Fibroblast activation protein-positive fibroblasts promote tumor progression through secretion of CCL2 and interleukin-6 in esophageal squamous cell carcinoma.
Chemokine C-C motif chemokine 2 (CCL2) and its receptor C-C chemokine receptor type 2 (CCR2) constitute a key signaling axis in inflammation that has recently attracted much interest on the basis of evidence showing its association with cancer progression.
While the importance of CCL2/CCR2 signaling in macrophages during cancer progression is well documented, we recently showed that CCL2-mediated breast cancer progression depends on CCR2 expression in carcinoma cells.
Moreover, CnP strongly decreased the various cytokines involved in cancer progression, such as interleukin (IL)-6, IL-8, C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine ligand 12 (CXCL12), secreted by CAF.
We selected genes for investigation based on their potential role in wound healing (AQP3), rash development (CCL2), fibroblast activation (PALLD), cancer and cancer progression (GDF-15, SLC7A11, MMP12, and DIRAS3), and cell cycle control (CDC6).
Moreover, HFD-induced DPP4 activity facilitated angiogenesis and cancer cell metastasis in vitro and in vivo, and vildagliptin prevented tumor progression by mediating the pro-angiogenic role of chemokine ligand 2 (CCL2).
Our results suggest that FOXK1 directly links mTORC1 signaling and CCL2 expression in a manner independent of NF-κB and that CCL2 produced by this pathway contributes to tumor progression.
Nude mice bearing MCF10CA1d breast tumor xenografts were implanted with osmotic pumps containing control IgG or anti-CCL2 and analyzed for CCL2 levels and tumor progression over 4 weeks.
The CCL2-CCR2 chemokine axis has an important role in cancer progression where it contributes to metastatic dissemination of several cancer types (e.g., colon, breast, prostate).
CCL2 has also been found to be expressed in various cancers, including human hepatoma cells, human cancer progression, and human multiple myeloma cells.
Nuclear factor-kappaB (NF-κB) and CCL2/CCR2 chemokine axis play a central role in tumor progression such as stimulation of angiogenesis, acceleration of tumor invasion and migration, and suppression of innate immunosurveillance in the macrophage-related functions.
Monocyte chemotactic protein‑1 (MCP‑1/CCL2) is an important immune factor, which may be important in cancer progression by promoting proliferation, invasion, metastasis and the tumor microenvironment.
Circulating concentrations of the cytokines interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF) and chemokines monocyte chemotatic protein 1 (MCP-1)/CCL2 and growth-regulator oncogene α (GROα)/chemokine C-X-C motif ligand 1 are commonly increased in cancer patients and they are increasingly recognised as important promoters, via divergent mechanisms, of cancer progression and metastasis.
Most importantly, we show for the first time that BMM-supplied CTSK may be involved in CCL2- and COX-2-driven pathways that contribute to tumor progression in bone.
Malignant ascites significantly enhanced the release of cytokines/chemokines, which have been previously shown to support tumour progression, such as interleukin (IL)-6, IL-1β, CCL2 and CXCL8, in human peripheral blood mononuclear cells of healthy volunteers.