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Expression profiling in hypoxic non-small cell lung cancer

Abstract

Lung cancer is the leading cause of cancer deaths overall in the world. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancers. Overall survival is poor, in part due to resistance to chemotherapy and radiotherapy. Intratumoral hypoxia (limited oxygen supply) frequently occurs in solid tumors, such as NSCLC. Hypoxia initiates adaptive responses in tumor cells and was shown to induce chemotherapy resistance and promote aggressive tumor growth. The mechanisms of hypoxia-induced adaptive responses in solid tumors are not fully elucidated, yet. We established an ex-vivo model for hypoxic adaptation using NSCLC surgery fragments. The fragments are maintained in short-time culture in hypoxia or ambient oxygen (normoxia) without significant loss of viability or increase in apoptosis and display significant induction of carbonic anhydrase IX, a marker for tumor hypoxia, under hypoxic conditions. The aim of the current study is to analyze hypoxia-induced gene expression changes using cDNA microarrays and consecutive single gene real-time polymerase chain reaction (RT-PCR) on hypoxic vs. normoxic NSCLC fragments, in order to identify genes that are consistently induced or suppressed in hypoxia. Our study thus provides a novel approach to identify molecular pathways that are crucial for hypoxic adaptive changes in NSCLC and might represent targets for therapy.

Keywords

respiratory medicine

Project Leader:

Leithner Katharina

Duration:

01.01.2010-31.12.2011

Type of Research

basic research

Staff

Leithner, Katharina, Project Leader

Frille, Armin, Co-worker

MUG Research Units

Core Facility Molecular Biology

Department of Anesthesiology and Intensive Care Medicine

Diagnostic and Research Institute of Pathology

Division of Respiratory Medicine

Division of Thoracic and Hyperbaric Surgery

Funded by

Medizinische Universität Graz, Stiftingtalstraße 6, 8010 Graz, Austria

Project results published

> Hypoxia increases membrane metallo-endopeptidase e... BMC Cancer. 2014; 14(1):40-40

> The metallopeptidase neprilysin is a hypoxia-induc... European Respiratory Journal . 2012; 40 Suppl. 56: P4167--22nd Annual Congress ofthe European Respiratory Society; SEPT 1-5, 2012; Vienna.

> Expression of membrane metallo-endopeptidase (CD10... Abstract CD of the Cell Symposium Angiogenesis, Metabolic Regulation, and Cancer Biology. 2012; P1.48--Cell Symposium - Angiogenesis, Metabolic Regulation and Cancer Biology; July 6-8, 2012; Leuven, Belgium.

> Expression profiling in hypoxic non-small cell lun... European Respiratory Journal Supplement. 2011; P1964--European Respiratory Society Annual Congress; SEPT 24-28, 2011; Amsterdam, The Netherlands.

> Neprilysin is induced by hypoxia and is a prognost... WIEN KLIN WOCHENSCHR. 2011; 123(17-18):A24-A24.-Jahrestagung der Österreichischen Gesellschaft für Pneumologie; SEPT 8-10, 2011; Vienna, AUSTRIA.

> Expression profiling identifies neprilysin as a hy... Doctoral Day; NOV 4, 2011; Graz, AUSTRIA. 2011.

> Expression of key enzymes for gluconeogenesis and ... WIEN KLIN WOCHENSCHR. 2010; 122(21-22): A50-A50.

> Expression of key enzymes for gluconeogenesis and ... Abstract book, 2010; P17--Joint ZMF and Doctoral Days; NOV 4-6, 2010; Graz, AUSTRIA.