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Browsing by Author "Coelho, Filipa Lopes"

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  • Gluconeogenesis and amino acids metabolism in ovarian clear cell carcinoma
    Publication . Coelho, Filipa Lopes; Serpa, Jacinta; Tavares, Álvaro
    Tumor cells may exhibit different metabolic profiles compared to normal tissues from which they are derived. Those observations gave rise to the new concept that tumorigenesis requires metabolic alterations to sustain cell proliferation. Several studies reveal that increased cell proliferation is accompanied by increased glucose consumption. In OCCC, a typical morphological feature is the accumulation of glycogen in cancer cells cytoplasm this fact allows us to raise the stepwise questions: 1) Is glucose the main energy and carbon source used by OCCC?; 2) Being glucose a relevant energy and carbon source, can gluconeogenesis be working on ovarian clear cell carcinoma?, and 3) If gluconeogenesis is working on, which are the gluconeogenic substrates used by ovarian clear cell carcinoma? In the present thesis we try to clarify, in an OCCC in vitro model (ES2) and in a glucose privation microenvironment, if gluconeogenesis pathway is working on, in order to support cells energy demands. Glutamine, lactate and butyrate were testes as putative gluconeogenesis substrates. Metabolic analysis by NMR of ES2 cell line showed the presence of glycogen, characteristic of this cell line, though 13C unlabelled, meaning that it was not synthesized from the tested substrates. At the same time the tested time points were not enough to clarify if glucose is de novo synthesized through gluconeogenesis. Nevertheless, NMR results showed that glutaminolysis was the major pathway used to sustain ES2 cell proliferation, with the production of TCA intermediates, as well as intermediates for macromolecular synthesis. These findings prompted us to investigate the role of glutaminolysis in OCCC. In NMR analysis, we observed the synthesis of glycine and glutamate as well as the synthesis of GSH. Gathering cysteine to cells exposed to glutamine, we verified an increase in the synthesis of GSH. In cancer, GSH high levels is related to drug resistance which is in agreement with the fact that OCCC poor prognosis is also due to resistance to therapy. Summing up, amino acids can play a central role in OCCC concerning energy and carbon metabolism as well as drug resistance.
    2013Master thesis Open access Show more