title: Role of N-cadherin in proliferation, migration, and invasion of germ cell tumours.
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.
authors.affiliation: Institute of Pathology, University of Göttingen, Göttingen, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Bremmer
authors.affiliation: Institute of Pathology, University of Göttingen, Göttingen, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Schallenberg
authors.affiliation: Department of Endocrinology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Jarry
authors.affiliation: Institute of Pathology, University of Göttingen, Göttingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Küffer
authors.affiliation: Department of Human Genetics, University of Göttingen, Göttingen, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Kaulfuss
authors.affiliation: Department of Human Genetics, University of Göttingen, Göttingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Burfeind
authors.affiliation: Department of Urology, University of Göttingen, Göttingen, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Strauß
authors.affiliation: Department of Urology, University of Göttingen, Göttingen, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Thelen
authors.affiliation: Institute of Pathology, University of Göttingen, Göttingen, Germany.
authors.forename: Heinz Joachim
authors.initials: HJ
authors.lastname: Radzun
authors.affiliation: Institute of Pathology, University of Göttingen, Göttingen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Ströbel
authors.affiliation: Department of Oncology, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.|Tumour and Breast Center ZeTuP, St. Gallen, Switzerland.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Honecker
authors.affiliation: Institute of Pathology, University of Göttingen, Göttingen, Germany.
authors.forename: Carl Ludwig
authors.initials: CL
authors.lastname: Behnes
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015820:Cadherins / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D002945:Cisplatin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D015820:Cadherins; D002945:Cisplatin
keywords: GCT-cell lines; N-cadherin; cisplatin resistance; germ cell tumours