Blockade of CCL2/CCR2 signalling with knockout of CCR2 or with a CCR2 antagonist inhibits malignant growth and metastasis, reduces postsurgical recurrence, and enhances survival.
In this study, we provide evidence of a lateral transmission of aggressive features between aggressive and non-aggressive tumor cells, consisting of gain of expression of cancer stem cell markers, increased expression of CXCL12 receptors CXCR4 and CXCR7 and increased invasiveness in response to CXCL12, which correlated with high levels of secretion of pro-inflammatory mediators G-CSF, GM-CSF, MCP-1, IL-8 and metalloproteinases 1 and 2 by the aggressive cells.
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).
Our results supported that CCL2 I/D gene variant contribute to the susceptibility and clinic-pathological characteristic of PCa and could be considered as an important risk factor for this malignancy in North Indian men.
Together, these results suggest that FBXW7 antagonizes cancer development in not only a cell-autonomous manner, but also a non-cell-autonomous manner, and that modulation of the FBXW7/NOTCH/CCL2 axis may provide a potential approach to suppression of cancer metastasis.
Genetic models analysis revealed a significant association between MCP-1-2518 A/G polymorphism and cancer risk in homozygous co-dominant (OR=2.06, 95%CI, 1.06-3.98; p=0.03) and recessive (OR=1.97, 95%CI, 1.05-3.70; p=0.03) models.
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.
Overall, MCP-1 and CCR2 polymorphisms showed no significant associations with cancer risk (MCP-1-2518A/G, GG + GA vs. AA: OR=0.94, 95% CI=0.76-1.17; CCR2 V64I, AA+AG vs. GG: OR=1.27, 95% CI=0.87-1.86).
These data suggested that MCP-1-2518A/G and CCR2 190G/A polymorphisms are new risk factors for RCC and could be used as prognostic markers for this malignancy.
This meta-analysis suggested that the 2518A/G polymorphism of MCP-1 gene is associated with risk of cancer among Asian, but not in Caucasian populations.
The -2518A/G polymorphism in the regulatory region of the monocyte chemo-attractant protein-1 (MCP-1) gene has been reported to be associated with cancer risk.
In addition, irradiated meningioma cancer cell conditioned medium (CM) showed an increased ability to attract HMEC and to stimulate MCP-1-induced protein (MCPIP), VEGF and angiogenin expression in HMEC.
COPD group had higher plasma MCP1 levels than healthy participants (257.0 versus 194.4 pg/mL) in the univariate analysis (P = .005); and in stepwise liner regression analysis after adjustment for age, alcohol, body mass index, cancer history, and steroid use (P = .002; 95% confidence interval [CI]: 30.72-128.02).
In this chapter, targeting CCL2 in prostate cancer will be used as an example to show translation of laboratory findings from cancer molecular biology to the clinic.