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Zur Rolle von N-Cadherin in der Proliferation, Migration und Invasion maligner Keimzelltumoren des Hodens

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

Simon Schallenberg
Doctoral thesis
Date of Examination: 2019-12-12
Date of issue: 2019-11-19
Advisor: Bremmer, Felix PD Dr.
Referee: Schön, Margarete Prof. Dr.
Referee: Meyer, Thomas Prof. Dr.

Persistent Address: http://hdl.handle.net/21.11130/00-1735-0000-0005-12AD-4

 

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Abstract

English

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. 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
Keywords: GCT-cell lines; germ cell tumours; cisplatin resistance; migration; invasion; proliferation; N-cadherin
Schlagwörter: Keimzelltumorzelllinien; Keimzelltumoren; Cisplatin-Resistenz; Migration; Invasion; Proliferation; N-Cadherin
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