Establishment and comparative characterization of novel squamous cell non-small cell lung cancer cell lines and their corresponding tumor tissue
| Autor: | Thomas Muley, Holger Sültmann, Anna Jauch, Hans Hoffmann, Karin Mueller-Decker, Hendrik Dienemann, Martin Granzow, Michael Meister, Elizabeth Chang Xu, Esther Herpel, Sandra Gottschling, Philipp A. Schnabel, Felix J.F. Herth, Ruprecht Kuner, Christian Bender, Thomas Efferth |
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| Rok vydání: | 2010 |
| Předmět: |
Pulmonary and Respiratory Medicine
Cancer Research Lung Neoplasms Angiogenesis Carcinogenicity Tests Cell In situ hybridization Cell Growth Processes Biology medicine.disease_cause Mice Cell Movement Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Cell Adhesion Animals Humans Cell Lineage In Situ Hybridization Fluorescence Mutation Comparative Genomic Hybridization medicine.diagnostic_test Neovascularization Pathologic Gene Expression Profiling Cell Differentiation medicine.disease Primary tumor Molecular biology DNA Fingerprinting Gene expression profiling ErbB Receptors medicine.anatomical_structure Genes ras Oncology Cell culture Tandem Repeat Sequences Lymphatic Metastasis Carcinoma Squamous Cell Fluorescence in situ hybridization |
| Zdroj: | Lung cancer (Amsterdam, Netherlands). 75(1) |
| ISSN: | 1872-8332 |
| Popis: | 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. Materials and 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. |
| Databáze: | OpenAIRE |
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