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Updated: Feb 6, 2026
Merkel Cell Polyomavirus Infection and Detection
Published on: February 7, 2019
CCL17/TARC and CCR4 expression in Merkel cell carcinoma
Kashif Rasheed1, Ibrahim Abdulsalam1, Silje Fismen2
1Molecular Inflammation Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, N-9037, Tromsø, Norway.
Abstract:
Merkel cell carcinoma (MCC) is a rare, highly aggressive neuroendocrine skin cancer. In more than 80% of the cases, Merkel cell polyomavirus (MCPyV) is a causal factor. The oncogenic potential of MCPyV is mediated through its viral oncoproteins, large T antigen (LT) and small t antigen (sT). To investigate the role of cytokines in MCC, a PCR array analysis for genes encoding inflammatory cytokines and receptors was performed on MCPyV-negative and MCPyV-positive MCC cell lines, respectively. We detected an increased expression of CCL17/TARC in the MCPyV-positive MKL2 cell line compared to the MCPyV-negative MCC13 cell line. Transfection studies in MCC13 cells with LT expression plasmid, and a luciferase reporter plasmid containing the CCL17/TARC promoter, exhibited stimulated promoter activity. Interestingly, the ectopic expression of CCL17/TARC upregulated MCPyV early and late promoter activities in MCC13 cells. Furthermore, recombinant CCL17/TARC activated both the mitogen-activated protein kinase and the NF-κB pathways. Finally, immunohistochemical staining on human MCC tissues showed a strong staining of CCL17/TARC and its receptor CCR4 in both LT-positive and -negative MCC. Taken together, CCL17/TARC and CCR4 may be a potential target in MCC therapy providing MCC patients with a better overall survival outcome.
Insights
Merkel cell carcinoma (MCC), often caused by Merkel cell polyomavirus (MCPyV), involves the cytokine CCL17/TARC. Targeting CCL17/TARC and its receptor CCR4 may offer new therapeutic strategies for MCC patients.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer.
- Merkel cell polyomavirus (MCPyV) is implicated in over 80% of MCC cases.
- MCPyV's oncogenic potential is linked to its large T antigen (LT) and small t antigen (sT) oncoproteins.
Purpose of the Study:
- To investigate the role of cytokines in MCC pathogenesis.
- To explore the relationship between MCPyV and cytokine expression in MCC.
- To evaluate CCL17/TARC and CCR4 as potential therapeutic targets in MCC.
Main Methods:
- PCR array analysis of cytokine and receptor genes in MCC cell lines.
- Transfection studies to assess the effect of MCPyV LT on CCL17/TARC promoter activity.
- Luciferase reporter assays to measure promoter activity.
- Immunohistochemical staining of human MCC tissues for CCL17/TARC and CCR4.
Main Results:
- Increased CCL17/TARC expression was observed in MCPyV-positive MCC cells.
- MCPyV LT stimulated CCL17/TARC promoter activity.
- CCL17/TARC expression upregulated MCPyV promoter activity.
- Recombinant CCL17/TARC activated MAPK and NF-κB pathways.
- CCL17/TARC and CCR4 were expressed in human MCC tissues, regardless of LT status.
Conclusions:
- CCL17/TARC plays a significant role in MCC, potentially influenced by MCPyV.
- The CCL17/TARC/CCR4 axis is a promising therapeutic target for MCC.
- Targeting this pathway could improve patient survival outcomes in MCC.
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