Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Lesko, J.
Metabolism in lung cancer: Ex vivo analysis with stabile isotope labelled tracers
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2018. pp. 46
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Hrzenjak Andelko
- Leithner Katharina
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- Abstract:
- The metabolism of tumour cells is adapted to rapid cell division. Increased lipid synthesis, particularly of phospholipids as component of cell membranes, is crucial for cell proliferation. Thus, metabolic pathways are intensively studied as potential therapeutic approach for cancer treatment, however they are highly influenced by tumour-specific microenvironment in vivo. Research in ex vivo tissue models may provide new findings. The aim of this study was to establish an ex vivo model that allows to investigate phospholipid synthesis in lung cancer cells under physiological conditions. Tissue fragments from fresh lung and preoperative untreated non-small cell lung cancer (NSCLC) of seven patients were cultured for 72 hours. In tracer experiments using these samples, we analysed the conversion of 13C6 glucose and 13C5 glutamine into the glycerol moiety of phospholipids. Glucose provides the glycerol-backbone of phospholipids via glycolysis, while glutamine is potentially metabolised to glycerol-phosphate via glyceroneogenesis. The concentration of 13C6 glucose in the media corresponded to physiological (5 mM) or nutrient-poor, tumour-specific (1 mM) conditions. Incorporation of labelled carbons into the glycerol moiety was analysed by liquid chromatography and mass spectrometry. Fragment viability, measured after several time intervals, was variable. However, viable tissue was present in all samples during the entire experimental course. Tumour fragments showed more necrotic changes compared with lung fragments after 72 hours. An incorporation of 13C6 glucose into the phospholipid-linked glycerol (yielding a glycerol-fragment with three 13C) was detected both in tumour and lung fragments. Interestingly, the rate of incorporation into lung or tumour tissue was similar. The control group with unlabelled glucose did not show any enrichment. Independent of the nutrient content, 13C5 glutamine was not converted into the glycerol moiety. This ex vivo model is well suited for studying the conversion of 13C6 glucose into the glycerol backbone of phospholipids in fresh lung and tumour fragments. By using patient-derived tissue in its three-dimensional context in patho-/physiological nutrient conditions, this model enables investigating tumour metabolism under conditions mimicking the situation in vivo. As a limitation, ex vivo culture impairs tissue viability. Shorter incubation time and improved culture conditions (shaking or rocking, etc.) might enhance fragment viability.