title: Establishment and Characterization of a Pair of Patient-derived Human Non-small Cell Lung Cancer Cell Lines from a Primary Tumor and Corresponding Lymph Node Metastasis.
abstract: BACKGROUND
  Non-small lung cancer is the leading cause of cancer-related mortality worldwide. For a deeper understanding of tumor biology, we established a pair of cell lines derived from a primary tumor and a corresponding lymph node metastasis.
  
  
  METHODS
  The cell line BC4323 from the primary tumor (PT) and a mediastinal lymph node metastasis (LN) were derived from an adenocarcinoma (pT2, pN2, G3, UICC stage IIIa) in a 47-year-old female patient. Comparative characterization was performed by in vitro analysis. A murine xenograft was established for analysis of in vivo behavior.
  
  
  RESULTS
  Chromosomal aberrations were detected in multiple chromosomal sections throughout the entire genome, with only a few differences between PT and LN cells. High-level Kirsten ras oncogene homolog (KRAS) mutation and amplification were seen based on a chromosomal translocation and novel assembled chromosome. In contrast to the genomic level, at the mRNA and protein levels, multiple differences were detectable, in particular in markers for cell adhesion [e.g. epithelial cell adhesion molecule (EpCAM), CD44, P-selectin binding, epidermal growth factor receptor (EGFR) and integrin alphaV] and the epithelial-mesenchymal transition. Due to accelerated tumor growth in vivo by the PT cells, a shortened overall survival was seen (60 vs. 101 days, p=0.005).
  
  
  CONCLUSIONS
  We provide detailed analysis of a cell line derived from a primary tumor and a corresponding LN metastasis. This unique feature allows further investigative analysis of the differences and regulatory processes underlying the metastatic process during tumor progression in non-small cell lung cancer.
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany Institute of Anatomy and Experimental Morphology, University Cancer Center Hamburg, University of Hamburg, Hamburg, Germany fgebauer@uke.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Gebauer
authors.affiliation: Institute of Anatomy and Experimental Morphology, University Cancer Center Hamburg, University of Hamburg, Hamburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wicklein
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Tachezy
authors.affiliation: Institute for Pathology, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Grob
authors.affiliation: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Steinemann
authors.affiliation: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: Georgi
authors.initials: G
authors.lastname: Manukjan
authors.affiliation: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Göhring
authors.affiliation: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.affiliation: Institute of Anatomy and Experimental Morphology, University Cancer Center Hamburg, University of Hamburg, Hamburg, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Maar
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bockhorn
authors.affiliation: Institute of Anatomy and Experimental Morphology, University Cancer Center Hamburg, University of Hamburg, Hamburg, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Schumacher
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D008207:Lymphatic Metastasis / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D010641:Phenotype
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins
keywords: CD44; EGFR; EpCAM; KRAS; Non-small cell lung cancer; P-selectin; cell line; chromosomal aberrations; epithelial mesenchymal transition; integrin alpha V; lymph node metastases