Oncotarget

Research Papers:

Role of N-cadherin in proliferation, migration, and invasion of germ cell tumours

Felix Bremmer _, Simon Schallenberg, Hubertus Jarry, Stefan Küffer, Silke Kaulfuss, Peter Burfeind, Arne Strauß, Paul Thelen, Heinz Joachim Radzun, Philipp Ströbel, Friedemann Honecker and Carl Ludwig Behnes

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Oncotarget. 2015; 6:33426-33437. https://doi.org/10.18632/oncotarget.5288

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Abstract

Felix Bremmer1,*, Simon Schallenberg1,*, Hubertus Jarry2, Stefan Küffer1, Silke Kaulfuss3, Peter Burfeind3, Arne Strauß4, Paul Thelen4, Heinz Joachim Radzun1, Philipp Ströbel1, Friedemann Honecker5,6, Carl Ludwig Behnes1

1Institute of Pathology, University of Göttingen, Göttingen, Germany

2Department of Endocrinology, University Medical Center Göttingen, Göttingen, Germany

3Department of Human Genetics, University of Göttingen, Göttingen, Germany

4Department of Urology, University of Göttingen, Göttingen, Germany

5Department of Oncology, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany

6Tumour and Breast Center ZeTuP, St. Gallen, Switzerland

*These authors have contributed equally to this work

Correspondence to:

Felix Bremmer, e-mail: felix.bremmer@med.uni-goettingen.de

Keywords: N-cadherin, cisplatin resistance, germ cell tumours, GCT-cell lines

Received: July 07, 2015     Accepted: September 22, 2015     Published: October 02, 2015

ABSTRACT

Germ cell tumors (GCTs) are the most common malignancies in young men. Most patients with GCT can be cured with cisplatin-based combination chemotherapy, even in metastatic disease. In case of therapy resistance, prognosis is usually poor. We investigated the potential of N-cadherin inhibition as a therapeutic strategy. We analyzed the GCT cell lines NCCIT, NTERA-2, TCam-2, and the cisplatin-resistant sublines NCCIT-R and NTERA-2R. Effects of a blocking antibody or siRNA against N-cadherin on proliferation, migration, and invasion were investigated. Mouse xenografts of GCT cell lines were analyzed by immunohistochemistry for N-cadherin expression. All investigated GCT cell lines were found to express N-cadherin protein in vitro and in vivo. Downregulation of N-cadherin in vitro leads to a significant inhibition of proliferation, migration, and invasion. N-cadherin-downregulation leads to a significantly higher level of pERK. N-cadherin-inhibition resulted in significantly higher rates of apoptotic cells in caspase-3 staining. Expression of N-cadherin is preserved in cisplatin-resistant GCT cells, pointing to an important physiological role in cell survival. N-cadherin-downregulation results in a significant decrease of proliferation, migration, and invasion and stimulates apoptosis in cisplatin-naive and resistant GCT cell lines. Therefore, targeting N-cadherin may be a promising therapeutic approach, particularly in cisplatin-resistant, therapy refractory and metastatic GCT.


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