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Int J Cancer. 2017 Jul 1;141(1):160-171. doi: 10.1002/ijc.30723. Epub 2017 Apr 21.

Spontaneous lung metastasis formation of human Merkel cell carcinoma cell lines transplanted into scid mice.

Author information

1
Institute of Anatomy and Experimental Morphology, University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
2
Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
3
Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
4
Heinrich-Pette Institute, Leibniz Institute for Experimental Virology, Research Group Virus Genomics, Hamburg, Germany.
5
Department of Oral and Maxillofacial Surgery, Charité Universitätsmedizin Berlin, Germany.
6
Department of Dermatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Abstract

Merkel cell carcinoma (MCC) is an aggressive skin cancer entity that frequently leads to rapid death due to its high propensity to metastasize. The etiology of most MCC cases is linked to Merkel cell polyomavirus (MCPyV), a virus which is monoclonally integrated in up to 95% of tumors. While there are presently no animal models to study the role of authentic MCPyV infection on transformation, tumorigenesis or metastasis formation, xenograft mouse models employing engrafted MCC-derived cell lines (MCCL) represent a promising approach to study certain aspects of MCC pathogenesis. Here, the two MCPyV-positive MCC cell lines WaGa and MKL-1 were subcutaneously engrafted in scid mice. Engraftment of both MCC cell lines resulted in the appearance of circulating tumor cells and metastasis formation, with WaGa-engrafted mice showing a significantly shorter survival time as well as increased numbers of spontaneous lung metastases compared to MKL-1 mice. Interestingly, explanted tumors compared to parental cell lines exhibit an upregulation of MCPyV sT-Antigen expression in all tumors, with WaGa tumors showing significantly higher sT-Antigen expression than MKL-1 tumors. RNA-Seq analysis of explanted tumors and parental cell lines furthermore revealed that in the more aggressive WaGa tumors, genes involved in inflammatory response, growth factor activity and Wnt signalling pathway are significantly upregulated, suggesting that sT-Antigen is the driver of the observed differences in metastasis formation.

KEYWORDS:

Merkel cell cancer; Merkel cell polyomavirus; metastasis formation; transcriptome analysis; xenograft scid mouse

PMID:
28380668
DOI:
10.1002/ijc.30723
[Indexed for MEDLINE]
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