Quantification of the chemokines CCL17 and CCL22 in human colorectal adenocarcinomas

Abstract

Abstract. Chemokines are believed to play a crucial role in local immunoresponse by regulating leukocyte movement in various tissues, including the intestinal mucosa. It has been suggested that they are key players in cancer biology, and several studies have identified leukocyte infiltration as a hallmark of most cancers. The chemokines CCL17 and CCL22 attract CCR4-bearing cells, which are especially polarised to Th2-type cells and regulatory T cells (Treg). Recent studies have revealed the participation of the CCL17 and CCL22 proteins in diseases such as atopic dermatitis and lymphoma. The purpose of this study was to assess the role of CCL17 and CCL22 protein expression in colorectal cancer (CRC) and to ascertain whether an association exists between promoter -431C>T CCL17 and -961G>A CCL22 gene polymorphisms in CRC versus non-CRC subjects. Using the ELISA assay, we noted a significantly higher expression of CCL22 in tumour tissue with a 2.3-fold up-regulation (tumour vs. paired normal tissue, n=78) but no significant difference in CCL17 protein expression. Immunohistochemistry revealed protein expression of CCL22 and CCL17 in the epithelial compartment of cancer tissue, in epithelial cells at the resection border that reflects normal tissue, and in some stromal cells such as lymphocytes, macrophages, and fibroblasts. Using a TaqMan system we screened for -431C>T CCL17 and -961G>A CCL22 gene variants in 245 CRC patients and 256 controls, but could not find any significant difference in genotype distribution or in allelic frequencies between the two groups. The genotype and allelic distributions of CRC patients were not related to tissue levels of CCL17 and CCL22 protein, and none of the variables were associated with plasma levels or clinical characteristics. To ascertain whether the tissue expression of CCL17 and CCL22 exerts an influence on the pathogenesis of CRC, a forthcoming study on the 5-year survival rate of CRC patients will be conducted. IntroductionChemokines are chemotactic cytokines that participate in the migration of various types of inflammatory cells and play an important role in the local immunoregulation of various tissues, including the intestinal mucosa (1-3). In general, chemokines are thought to be key players in cancer biology (4). Studies have demonstrated that leukocyte infiltration is a hallmark of most cancers (5-7) and promotes and regulates tumour growth, including metastasis and angiogenesis (8,9). T cell infiltration has been shown to be associated with a favourable prognosis in colorectal cancer (CRC) (10,11).The chemokines CCL17 and CCL22 have been the subject of immunogene therapy studies in murine models of colon carcinoma (12). The chemokine CCL17, also referred to as TARC (thymus-and activation-regulated chemokine), is a member of the CC chemokine group that is expressed in the thymus, dendritic cells, endothelial cells, colon tissue, keratinocytes and fibroblasts (13-17). Moreover, CCL17 is a ligand for CC chemokine receptor 4 (CCR4) and attracts CCR4 + cells (18,19). It...

Evaluating the Serum Levels of CCL17, CCL22, and CCL28 Chemokines and the Gene Expression of α4β1 and α4β7 Integrins in Patients With Allergic Rhinitis

“…Furthermore, a previous study showed elevated CCL17 and CCL22 levels in supernatants of bronchial mucosa biopsy cultures of patients with asthma after the allergen challenge (36). Another study in 2008 also showed a significantly high expression level of CCL22, but not CCL17, in colorectal cancerous tissues, compared to paired normal tissue from colorectal cancer patients (37). Our results indicated a significant increase in CCL22 serum levels in the patient group; however, there was no significant difference in CCL17 serum levels between allergic rhinitis patients and the control group.…”

Downstream STING pathways IRF3 and NF-κB differentially regulate CCL22 in response to cytosolic dsDNA

“…Taken together, these studies clearly show that our understanding of the variables in uencing CCL22 regulation remains incomplete, and this is especially true with respect to human cancers and nucleic acid sensing. Indeed, CCL22 expression was previously thought to be absent in malignant cells, but several studies including our own have shown that CCL22 can be expressed in these cells (39,54,84,85,(123)(124)(125)(126).…”

Transcriptome Analysis of Diffuse Large B-Cell Lymphoma Cells Inducibly Expressing MyD88 L265P Mutation Identifies Upregulated CD44, LGALS3, NFKBIZ, and BATF as Downstream Targets of Oncogenic NF-κB Signaling

“…The following supporting information can be downloaded at: . References [ 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 ] are cited in the supplementary materials.…”