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Amoedo 2014 Abstract MiP2014
Additional label MiP2014  +
Coupling states OXPHOS  +
Diseases Cancer  +
Event B3  + , Oral  +
Has abstract Many tumor cells show enhanced aerobic gly
Many tumor cells show enhanced aerobic glycolysis, even in the presence of oxygen: The so called Warburg effect. This pathway provides substrates for the synthesis of lipids, proteins and DNA. However, the Warburg effect does not necessarily imply mitochondrial dysfunction. Research currently pictures tumors as compositions of different populations of cells with distinct metabolic phenotypes, which are able to adjust to oxygen and nutrient gradients within the tumor mass. Not all cancer cells display a high glycolytic flux as proposed by Warburg. Our results indicate that progression to metastasis requires mitochondrial function. Our research, centered on cell lines that display increasing degrees of malignancy, focuses on metabolic events, especially those involving mitochondria, which could reveal which stages are mechanistically associated to metastasis. The experimental model consisted of murine melanocytes. These cells were subjected to several cycles of adhesion impediment, producing stable cell lines exhibiting phenotypes representing a progression from non-tumorigenic to metastatic cells. These were: non-tumorigenic cells melan-a (ma), non-tumorigenic cell line 4C (obtained after four cycles of adherence abrogation), non-metastatic 4C11- and metastatic 4C11+ melanoma cell lines. The metabolic profile of each of these different cell lines was investigated by evaluating enzymatic activities and expression of members of the glycolytic and oxidative pathways [1]. Our results show that only metastatic cell line (4C11+) released the highest amounts of lactate and exhibited high LDH activity related to glutamine catabolism. Results from measurements with high-resolution respirometry (HRR) show that 4C11+ intact cells increased (2.8x) oxidative metabolism, with enhanced (2.6x) rates of oxygen consumption coupled to ATP synthesis, when compared to the other pre-malignant stages. We did not observe an increase in mitochondrial content, mitochondrial biogenesis and alterations of mitochondrial morphology. In addition, in 4C11+ cells, we observed an increase in succinate oxidation (Complex II) and fatty-acid oxidation. Additional results suggest that lipid droplets may function as an extra source of fatty acids for mitochondrial β-oxidation. These results suggest that mitochondria of tumor cells could function as energy- and redox sensors to maintain metastases. We hypothesize that the oxidative metabolism of tumor cells in connection with the inactivation of anoikis may have been co-opted through a non-adaptive evolutionary process [2]. Detailed analysis of patterns in this and other models of tumor progression may reveal whether the modulation of the oxidative metabolism is a feature of the metastatic process.
sm is a feature of the metastatic process.  +
Has title The metabolic panorama during tumor progression towards malignancy.  +
Instrument and method Oxygraph-2k  +
MiP area Respiration  +
Pathways F  + , S  +
Preparation Permeabilized cells  +
Respiration and regulation Aerobic glycolysis  + , ATP production  + , Fatty acid  +
Tissue and cell Other cell lines  +
Was published by MiPNetLab BR Rio de Janeiro Rumjanek FD + , BR Rio de Janeiro Galina A +
Was submitted in year 2014  +
Was submitted to event MiP2014 +
Was written by Amoedo ND + , Rodrigues MF + , Pereira S + , Melo F + , Jasiulionis M + , Galina A + , Rumjanek FD +
Categories Abstracts
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
08:30:22, 9 November 2016  +
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