Role of N-cadherin in proliferation, migration, and invasion of germ cell tumours
2015 | journal article. A publication with affiliation to the University of Göttingen.
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Role of N-cadherin in proliferation, migration, and invasion of germ cell tumours
Bremmer, F.; Schallenberg, S.; Jarry, H.; Kueffer, S.; Kaulfuss, S.; Burfeind, P. & Strauss, A. et al. (2015)
Oncotarget, 6(32) pp. 33426-33437. DOI: https://doi.org/10.18632/oncotarget.5288
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Details
- Authors
- Bremmer, Felix; Schallenberg, Simon; Jarry, Hubertus; Kueffer, Stefan; Kaulfuss, Silke; Burfeind, Peter; Strauss, Arne; Thelen, Paul; Radzun, Heinz Joachim; Stroebel, Philipp; Honecker, Friedemann; Behnes, Carl Ludwig
- 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.
- Issue Date
- 2015
- Status
- published
- Publisher
- Impact Journals Llc
- Journal
- Oncotarget
- ISSN
- 1949-2553
- Sponsor
- Gottingen University
Open-Access Publikationsfonds 2015