Oncotarget

Research Papers:

CCL17/TARC and CCR4 expression in Merkel cell carcinoma

Kashif Rasheed _, Ibrahim Abdulsalam, Silje Fismen, Øystein Grimstad, Baldur Sveinbjørnsson and Ugo Moens

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Oncotarget. 2018; 9:31432-31447. https://doi.org/10.18632/oncotarget.25836

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Abstract

Kashif Rasheed1, Ibrahim Abdulsalam1, Silje Fismen2, Øystein Grimstad3, Baldur Sveinbjørnsson1 and Ugo Moens1

1Molecular Inflammation Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, N-9037, Tromsø, Norway

2Department of Pathology, University Hospital of Northern Norway, N-9038, Tromsø, Norway

3Department of Dermatology, University Hospital of Northern Norway, N-9038, Tromsø, Norway

Correspondence to:

Kashif Rasheed, email: kashif.rasheed@uit.no

Keywords: Merkel cell carcinoma; inflammation; cytokines; CCL17/TARC; CCR4

Received: January 29, 2018    Accepted: July 12, 2018    Published: July 31, 2018

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.


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