We found that PLX4720 treatment downregulated tumorCcl2 gene expression and decreased tumorCCL2 expression in both Braf(V600E) mouse melanoma transplants and in de novo melanomas in a manner that was coincident with reduced tumor growth.
In association of genotypes with clinic-pathological grade of tumor, homozygous DD (OR = 7.40; P c = 0.042) and variant allele carrier ID + DD (OR = 2.42; P c = 0.036) genotypes of CCL2 gene conferred risk in high Gleason grade tumor of PCa.
Furthermore, women with mutant homozygote (AA) of MCP-1 SNP increased the risk of deep stromal invasion, large tumor diameter, and parametrium invasion of cervical cancer, when compared to those with wild homozygote GG or heterozygote GA.
Analysis of the CCL2 locus at 17q11.2-q12 showed loss of heterozygosity (LOH) in 70% of primary tumours, and this was significantly more common in tumours of advanced stage or grade.
In conclusion, the expression of CCL2 is significantly correlated with Snail expression and may be used as a predictive co-biomarker for patient prognosis and tumor aggressiveness in GC.
The tumorigenicity and in vivo tumor growth of MCP-1 gene-transfected PC-14 cells were similar to those of the parent cells or mock-transfected cells when tumor cells were injected into the s.c. space of NK cell-intact severe combined immunodeficient (SCID) mice.
Several studies including ours have identified the CCR2-CCL2 axis as the key driver of the mobilization of monocytic cells from the BM to the blood and later their colonization at the tumor site.
Notably, the expression levels of proinflammatory factors, mainly including macrophage colony stimulating factor (M-CSF), transforming growth factor-β (TGF-β), monocyte chemotactic protein-1 (MCP-1) and stromal-derived factor-1 (SDF-1), increased after treatment with tumour-conditioned supernatant, and blockade of MCP-1 or SDF-1 decreased the proportion of tumour infiltrated MDSCs in mice co-transplanted with liver stromal cells and tumour cells, but not in mice with only tumour cells injection.
In conclusion, HUMSCs expressing ISZ-sTRAIL might be an efficient therapeutic approach against lung cancer and MCP-1/CCR2 axis is essential for the tumor tropism of HUMSCs.
Therefore, CCL2 secreted from the tumor microenvironment may attract and interact with monocytes/macrophages, and favor Th2 accumulation by inducing CCL22 secretion.
Tumor epithelial cells (TEpCs) and spindle-shaped stromal cells, not associated with the vasculature, of patients with early breast cancer express osteoprotegerin (OPG), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), receptor activator of nuclear factor kappa B ligand, stromal cell derived factor-1, interleukin-6, macrophage colony stimulating factor, chemokine (C-C motif) ligand-2 (CCL-2) and their receptors at significantly higher levels compared with non-neoplastic breast tissues.
Therefore, therapy employing antagonists of MCP-1 in combination with other inhibitors of angiogenesis may achieve more comprehensive inhibition of tumor growth.
Our findings suggest that local production of MCP-1 in the tumor site increases the anti-P-gp antibody-dependent cell-mediated cytotoxicity, and the MCP-1 gene-induced modification of MDR human SCLC cells thereby enhances the antimetastatic effect of therapy with anti-P-gp antibody.
Furthermore, a lowering of T-helper type 2 cytokines, MCP-1, interleukin (IL)-4, IL-6, and IL-10 marked lower tumor burden and enhanced treatment efficacy.
Interestingly, 4T1 cells that metastasized to the lung constitutively expressed elevated levels of MCP-1, and intravenous injection of 4T1 cells producing a high level of MCP-1 resulted in increased tumor foci in the lung of WT and MCP-1(-/-) mice.
Specifically, we aimed to optimize the therapeutic efficacy of Flt3L/TK treatment in the RG2 model by overexpressing the following genes within the brain tumor microenvironment: 1) a TK mutant with enhanced cytotoxicity (SR39 mutant TK), 2) Flt3L-IgG fusion protein that has a longer half-life, 3) CD40L to stimulate DC maturation, 4) T helper cell type 1 polarizing dendritic cell cytokines interleukin-12 or C-X-C motif ligand 10 chemokine (CXCL)-10, 5) C-C motif ligand 2 chemokine (CCL2) or C-C motif ligand 3 chemokine (CCL3) to enhance dendritic cell recruitment into the tumor microenvironment, 6) T helper cell type 1 cytokines interferon-γ or interleukin-2 to enhance effector T-cell functions, and 7) IκBα or p65RHD (nuclear factor kappa-B [NF-κB] inhibitors) to suppress the function of Foxp3+ Tregs and enhanced effector T-cell functions.
Chemokine (C-C motif) ligand 2 (CCL2) has been shown to play an important role in the regulation of tumor cell growth, metastasis and host immune response.
We also show that dl922-947-mediated reduction of the monocyte-attracting chemokine CCL2 decreased monocyte chemotaxis in vitro and tumor macrophage density in vivo.
Tumor measurements were conducted weekly (until 22 weeks of age) and at sacrifice (23 weeks of age) in female C3(1)/SV40Tag and C3(1)/SV40Tag MCP-1 deficient mice to determine tumor numbers and tumorvolumes.
These data suggest that CCL2 produced by CAF may be involved in the recruitment of inflammatory cells, but may also directly regulate the growth of the tumor.