Role of N-cadherin in proliferation, migration, and invasion of germ cell tumours
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Role of N-cadherin in proliferation, migration, and invasion of germ cell tumours. / Bremmer, Felix; Schallenberg, Simon; Jarry, Hubertus; Küffer, Stefan; Kaulfuss, Silke; Burfeind, Peter; Strauß, Arne; Thelen, Paul; Radzun, Heinz Joachim; Ströbel, Philipp; Honecker, Friedemann; Behnes, Carl Ludwig.
in: ONCOTARGET, Jahrgang 6, Nr. 32, 20.10.2015, S. 33426-37.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Role of N-cadherin in proliferation, migration, and invasion of germ cell tumours
AU - Bremmer, Felix
AU - Schallenberg, Simon
AU - Jarry, Hubertus
AU - Küffer, Stefan
AU - Kaulfuss, Silke
AU - Burfeind, Peter
AU - Strauß, Arne
AU - Thelen, Paul
AU - Radzun, Heinz Joachim
AU - Ströbel, Philipp
AU - Honecker, Friedemann
AU - Behnes, Carl Ludwig
PY - 2015/10/20
Y1 - 2015/10/20
N2 - 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.
AB - 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.
U2 - 10.18632/oncotarget.5288
DO - 10.18632/oncotarget.5288
M3 - SCORING: Journal article
C2 - 26451610
VL - 6
SP - 33426
EP - 33437
JO - ONCOTARGET
JF - ONCOTARGET
SN - 1949-2553
IS - 32
ER -