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SHR Neuro Krebs Kardio Lipid

Leithner, K; Wohlkoenig, C; Stacher, E; Lindenmann, J; Hofmann, NA; Gallé, B; Guelly, C; Quehenberger, F; Stiegler, P; Smolle-Jüttner, FM; Philipsen, S; Popper, HH; Hrzenjak, A; Olschewski, A; Olschewski, H.
Hypoxia increases membrane metallo-endopeptidase expression in a novel lung cancer ex vivo model - role of tumor stroma cells.
BMC Cancer. 2014; 14(1):40-40 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Gallé Birgit
Gülly Christian
Hofmann Nicole
Hrzenjak Andelko
Leithner Katharina
Lindenmann Jörg
Olschewski Andrea
Olschewski Horst
Popper Helmuth
Quehenberger Franz
Smolle-Juettner Freyja-Maria
Stacher-Priehse Elvira
Stiegler Philipp
Wohlkönig Christoph
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Abstract:
Hypoxia-induced genes are potential targets in cancer therapy. Responses to hypoxia have been extensively studied in vitro, however, they may differ in vivo due to the specific tumor microenvironment. In this study gene expression profiles were obtained from fresh human lung cancer tissue fragments cultured ex vivo under different oxygen concentrations in order to study responses to hypoxia in a model that mimics human lung cancer in vivo. Non-small cell lung cancer (NSCLC) fragments from altogether 70 patients were maintained ex vivo in normoxia or hypoxia in short-term culture. Viability, apoptosis rates and tissue hypoxia were assessed. Gene expression profiles were studied using Affymetrix GeneChip 1.0 ST microarrays. Apoptosis rates were comparable in normoxia and hypoxia despite different oxygenation levels, suggesting adaptation of tumor cells to hypoxia. Gene expression profiles in hypoxic compared to normoxic fragments largely overlapped with published hypoxia-signatures. While most of these genes were up-regulated by hypoxia also in NSCLC cell lines, membrane metallo-endopeptidase (MME, neprilysin, CD10) expression was not increased in hypoxia in NSCLC cell lines, but in carcinoma-associated fibroblasts isolated from non-small cell lung cancers. High MME expression was significantly associated with poor overall survival in 342 NSCLC patients in a meta-analysis of published microarray datasets. The novel ex vivo model allowed for the first time to analyze hypoxia-regulated gene expression in preserved human lung cancer tissue. Gene expression profiles in human hypoxic lung cancer tissue overlapped with hypoxia-signatures from cancer cell lines, however, the elastase MME was identified as a novel hypoxia-induced gene in lung cancer. Due to the lack of hypoxia effects on MME expression in NSCLC cell lines in contrast to carcinoma-associated fibroblasts, a direct up-regulation of stroma fibroblast MME expression under hypoxia might contribute to enhanced aggressiveness of hypoxic cancers.
Find related publications in this database (using NLM MeSH Indexing)
Apoptosis -
Biomarkers, Tumor - genetics
Carcinoma, Non-Small-Cell Lung - enzymology
Cell Hypoxia -
Cell Line, Tumor -
Cell Survival -
Fibroblasts - enzymology
Gene Expression Profiling - methods
Gene Expression Regulation, Enzymologic -
Gene Expression Regulation, Neoplastic -
Humans -
Lung Neoplasms - enzymology
Neprilysin - genetics
Oligonucleotide Array Sequence Analysis -
Stromal Cells - enzymology
Tissue Culture Techniques -
Up-Regulation -

Find related publications in this database (Keywords)
Hypoxia
Tumor
Expression array
Prognosis
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