Variable A-type lamin expression in Merkel cell carcinoma cell lines and its association with nuclear integrity

Scientific Reports, vol. 16

Abstract

Merkel cell carcinoma (MCC) is an aggressive type of neuro-endocrine skin cancer and can be subdivided into Merkel cell polyomavirus (MCPyV)-positive and MCPyV-negative cases. The nuclear lamina, consisting of A- and B-type lamins, is altered in different types of cancer and can be disrupted by viral infections. This study investigated A- and B-type lamin expression levels in MCPyV-negative and MCPyV-positive MCC cell lines in relation to the MCPyV status, using (live cell) imaging, qPCR, and Western blotting. MCPyV-positive MCC (non-adherent) cells showed lower A-type lamin and higher B-type lamin expression at both protein and mRNA levels as compared to MCPyV-negative (adherent) cells. Nuclear envelope (NE) ruptures were reversible in MCPyV-negative cells, while in MCPyV-positive cells these lead to cell death. Transfection of MCPyV-negative cells with small (sT) or large tumor (LT) antigens did not result in the expected decrease of A-type lamin expression. Future research into the correlation between A-type lamin expression levels and the different growth patterns, the occurrence of NE ruptures, the (lack of) NE repair in MCC cell lines, and the relation of lamin expression and tumor metastasis, will contribute to a better understanding of the molecular background of the aggressive phenotype of MCC.

Authors 7

1. Merel Stiekema corresponding

   Maastricht University Medical Centre

   Affiliation as printed

   Department of Genetics and Cell Biology, GROW-Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, Maastricht, The Netherlands. m.stiekema@maastrichtuniversity.nl

2. Charlotte van Gorp

   Maastricht University Medical Centre

   Affiliation as printed

   Department of Genetics and Cell Biology, GROW-Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, Maastricht, The Netherlands

3. Amanda Macamo

   Maastricht University · Maastricht University Medical Centre

   Affiliation as printed

   Department of Pathology, GROW-Research Institute for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, The Netherlands

4. Axel zur Hausen

   Maastricht University · Maastricht University Medical Centre

   Affiliation as printed

   Department of Pathology, GROW-Research Institute for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, The Netherlands

5. Marc A. M. J. van Zandvoort Aachen Institute for Molecular Cardiovascular Research IMCAR

   RWTH Aachen University · Maastricht University Medical Centre

   Affiliation as printed

   CARIM-Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands

   Department of Genetics and Cell Biology, GROW-Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, Maastricht, The Netherlands

   Institute for Molecular Cardiovascular Research IMCAR, RWTH Aachen University, Aachen, Germany

6. Frans C. S. Ramaekers

   Maastricht University Medical Centre

   Affiliation as printed

   Department of Genetics and Cell Biology, GROW-Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, Maastricht, The Netherlands

7. Jos L. V. Broers

   Maastricht University Medical Centre

   Affiliation as printed

   CARIM-Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands

   Department of Genetics and Cell Biology, GROW-Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, Maastricht, The Netherlands