Dataset Information

Reduced expression of chemokine (C-C motif) ligand-2 (CCL2) in ovarian adenocarcinoma.

ABSTRACT: Chemokine (C-C motif) ligand-2 (CCL2) is a chemoattractant and activator of macrophages and is a key determinant of the macrophage infiltrate into tumours. We demonstrate here that CCL2 is expressed in normal human ovarian surface epithelium (HOSE) cells and is silenced in most ovarian cancer cell lines, and silenced or downregulated in the majority of primary ovarian adenocarcinomas. 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. However, we did not detect any mutations in the CCL2 coding sequence in 94 primary ovarian adenocarcinomas. These data support the hypothesis that CCL2 may play a role in the pathobiology of ovarian cancers, but additional studies will be required to evaluate this possibility.

SUBMITTER: Arnold JM

PROVIDER: S-EPMC2361786 | biostudies-literature | 2005 Jun

REPOSITORIES: biostudies-literature

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Reduced expression of chemokine (C-C motif) ligand-2 (CCL2) in ovarian adenocarcinoma.

Arnold J M JM Huggard P R PR Cummings M M Ramm G A GA Chenevix-Trench G G

British journal of cancer 20050601 11

Chemokine (C-C motif) ligand-2 (CCL2) is a chemoattractant and activator of macrophages and is a key determinant of the macrophage infiltrate into tumours. We demonstrate here that CCL2 is expressed in normal human ovarian surface epithelium (HOSE) cells and is silenced in most ovarian cancer cell lines, and silenced or downregulated in the majority of primary ovarian adenocarcinomas. Analysis of the CCL2 locus at 17q11.2-q12 showed loss of heterozygosity (LOH) in 70% of primary tumours, and thi ...[more]

PMID: 15900302

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Project description:Introduction To a large extent, a person's susceptibility to developing periodontitis is determined by their genetic makeup. Research has shown that chemokines generated during an immune response can harm the periodontal ligaments, gingiva, and alveolar bone. Various chemokine genes located on different chromosomes contribute to periodontitis, and one such gene is C-C motif chemokine ligand 2 (CCL2), associated with the rs1024611 polymorphism, which is part of a cytokine gene cluster on the q-arm of chromosome 17. Objective Our specific objective was to investigate whether CCL2 polymorphisms could influence the relative risk of developing periodontitis. Building on these findings, we aimed to compare the frequency of a specific single nucleotide polymorphism (SNP) in the CCL2 gene between individuals with and without periodontitis. Materials and methods Fifty participants were enrolled in the study after obtaining informed consent and ethical clearance. Clinical assessments, including probing pocket depth, clinical attachment loss, and bleeding on probing, were utilized to classify individuals into two groups: a control group (Group A, n=25) and a periodontitis group (Group B, n=25). DNA extraction from collected samples involved drawing 2 ml of venous blood from the antecubital fossa and transferring it into a sterile tube with a pinch of ethylene diamine tetraacetic acid (EDTA) to prevent clotting. DNA extraction was performed and polymorphisms of CCL2 were assessed through polymerase chain reaction (PCR) and restriction enzyme digestion. Results The periodontitis group consisted of 25 patients, with an average age of 39.0±0.22 years, who met the American Academy of Periodontology's 2018 criteria for at least stage II periodontitis. The control group comprised 25 individuals with an average age of 41.3±0.49 years. Regarding the CCL2 gene polymorphism (rs1024611), there was no substantial variation in genotype frequencies between the patients and controls (p = 0.695). An agarose gel electrophoretogram, along with a standard DNA ladder, demonstrated partial amplification of the CCL2 gene spanning the polymorphism site (rs1024611). Genotypes observed were as follows: homozygous AA - 333 bp; heterozygous AG - 333 + 250 + 73 bp; homozygous GG - 250 + 73 bp. Conclusion In conclusion, there is no significant association between the CCL2 gene polymorphism rs1024611 and susceptibility to periodontitis.

Project description:Background and aimsHepatocellular carcinoma (HCC) is an aggressive malignancy which is often associated with a complex tumor microenvironment attributable to etiology-induced cellular inflammation. γδ T cells are known to detect and react to chronic inflammation, which is linked to cancer development, progression, and metastasis. Our recent genomic study revealed an increased infiltration of several immune cell types, including γδ T cells, in tumor microenvironments of a Thai HCC subtype associated with a good prognosis.Approach and resultsHere, we quantified the amount of γδ T cells using a γδ T-cell-specific gene signature in 247 Chinese HCC patients. We also validated the γδ T-cell signature in American HCC patients. Additionally, such an association was only found in tumor transcriptomic data, but not in adjacent nontumor transcriptomic data, suggesting a selective enrichment of γδ T cells in the tumor microenvironment. Moreover, the γδ T-cell signature was positively correlated with the expression of natural killer cell receptor genes, such as NKG2D and cytolytic T-cell genes granzymes and perforin, suggesting a stronger T-cell-mediated cytotoxic activity. Furthermore, we found that the γδ T-cell-specific gene expression is positively correlated with the expression of chemokine (C-C motif) ligand 4 (CCL4)/chemokine (C-C motif) ligand 5 (CCL5) and C-C chemokine receptor type 1 (CCR1)/C-C chemokine receptor type 5 (CCR5), the receptors for γδ T cells. We validated these results using immunohistochemical analysis of formalin-fixed, paraffin-embedded tumor biopsies from 182 HCC patients. Moreover, we found evidence of CCL4/CCL5-mediated recruitment of γδ T cells both in vitro and in a murine orthotopic Hepa1-6 HCC model.ConclusionsWe propose that CCL4/CCL5 may interact with their receptor, CCR1/CCR5, which may facilitate the recruitment of γδ T cells from peripheral blood or peritumor regions to the tumor regions. Consequently, an increasing infiltration of γδ T cells in tumors may enhance antitumor immunity and improve patients' prognosis.

Dataset Information

Reduced expression of chemokine (C-C motif) ligand-2 (CCL2) in ovarian adenocarcinoma.

Publications

Reduced expression of chemokine (C-C motif) ligand-2 (CCL2) in ovarian adenocarcinoma.

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