title: Establishment and comparative characterization of novel squamous cell non-small cell lung cancer cell lines and their corresponding tumor tissue.
abstract: BACKGROUND
  Cell lines play an important role for studying tumor biology and novel therapeutic agents. Particularly in pulmonary squamous cell carcinoma (SCC) the availability of cell lines is limited and knowledge about their representativeness for corresponding tumor tissue is scanty.
  
  
  METHODS
  We established three novel SCC cell lines from fresh tumor tissue of 28 donors, including 8 SCC. Two cell lines were derived from different localizations of the same donor, i.e. primary tumor and lymph node metastasis. This represents a so far unique combination in lung cancer. The genotypes, gene expression profiles and mutational status of epidermal growth factor receptor (EGF-R) and Kirsten rat sarcoma (k-ras) of the cell lines and their corresponding tumor tissue were analyzed and compared. Moreover, the molecular characteristics were related to functional properties of the cell lines. Those comprised proliferation, motility and chemosensitivity. The cell lines were authenticated by single tandem repeat DNA typing. Tumorigenicity was analyzed in a murine xenograft model.
  
  
  RESULTS
  Comparative genomic hybridization and multiplex fluorescence in situ hybridization revealed essential genetic similarities between the cell lines and their corresponding tumor tissue, but indicated also some genetic evolution and clonal selection. EGF-R or k-ras mutations were not detected. Gene expression profiling showed various differences between tumor tissue and cell lines affecting gene clusters associated with immune response, adhesion, proliferation, differentiation and angiogenesis. However, there were also common gene expression patterns reflecting the relationship between cell lines and their corresponding tumor tissue. Moreover, the molecular characteristics of the tumor tissue and the descendent cell line were associated with functional properties of the latter. All cell lines showed a unique, heterozygous human DNA profile and one cell line displayed rapid tumor formation in mice.
  
  
  CONCLUSIONS
  Here, we demonstrate that cell lines represent a useful in vitro system for studying basic mechanisms in lung cancer, but cover only distinct molecular characteristics of the original tumor. Moreover, we present three novel, comprehensively characterized SCC cell lines.
authors.affiliation: Dept. of Thoracic Oncology, Thoraxklinik/University of Heidelberg, Amalienstr. 5, 69126 Heidelberg, Germany. sandra.gottschling@thoraxklinik-heidelberg.de
authors.forename: Sandra
authors.initials: S
authors.lastname: Gottschling
authors.forename: Anna
authors.initials: A
authors.lastname: Jauch
authors.forename: Ruprecht
authors.initials: R
authors.lastname: Kuner
authors.forename: Esther
authors.initials: E
authors.lastname: Herpel
authors.forename: Karin
authors.initials: K
authors.lastname: Mueller-Decker
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Schnabel
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Xu
authors.forename: Thomas
authors.initials: T
authors.lastname: Muley
authors.forename: Holger
authors.initials: H
authors.lastname: Sültmann
authors.forename: Christian
authors.initials: C
authors.lastname: Bender
authors.forename: Martin
authors.initials: M
authors.lastname: Granzow
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
authors.forename: Hans
authors.initials: H
authors.lastname: Hoffmann
authors.forename: Hendrik
authors.initials: H
authors.lastname: Dienemann
authors.forename: Felix J F
authors.initials: FJ
authors.lastname: Herth
authors.forename: Michael
authors.initials: M
authors.lastname: Meister
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods; D016172:DNA Fingerprinting / Q000379:methods; D066246:ErbB Receptors / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D011905:Genes, ras; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D051379:Mice; D009154:Mutation; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020080:Tandem Repeat Sequences
chemical_list: D066246:ErbB Receptors