Lung cancer is the leading cause of cancer-related deaths in the U.S. For the majority of patients (70%), the extent of the disease precludes complete surgical resection and treatment relies solely on radiation, chemotherapy or a combination of both. Current therapy selection is based on the histopathologic examination of needle biopsies obtained during bronchoscopy. To complement current histopathological classification, we investigated the suitability of metabolomics to improve tumor classification. Initial data suggested the importance of glutamine (Gln). Gln is a known precursor for the TCA cycle and glutathione (GSH). To determine the role of Gln in lung tumorigenesis we investigated Gln metabolism and GSH synthesis in adenocarcinoma (AdenoCa) and squamous cell carcinoma (SqCCa) cell lines. The results suggest greater importance for GSH synthesis as compared to providing TCA building blocks. Subsequently, a second set of patient biopsies were evaluated for changes in Gln uptake and GSH synthesis. As expected, Gln depletion with the addition of GSH elevation were markers for cancer positive lymph nodes. Our data suggest that metabolomic profiling in lymph node fluids is a promising approach to identify the metabolic tumor phenotype. This novel approach complements histpathological diagnoses and enables mechanism-based therapy selection.

Importance of glutamine uptake and glutathione synthesis in lung tumorigenesis

248th National Meeting (2014)

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