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Molecular Cancer

, 7:79

First Online: 21 October 2008Received: 11 May 2008Accepted: 21 October 2008


BackgroundThe functional status of a cell is expressed in its metabolic activity. We have applied stable isotope tracing methods to determine the differences in metabolic pathways in proliferating Rhabdomysarcoma cells Rh30 and human primary myocytes in culture. Uniformly C-labeled glucose was used as a source molecule to follow the incorporation of C into more than 40 marker metabolites using NMR and GC-MS. These include metabolites that report on the activity of glycolysis, Krebs- cycle, pentose phosphate pathway and pyrimidine biosynthesis.

ResultsThe Rh30 cells proliferated faster than the myocytes. Major differences in flux through glycolysis were evident from incorporation of label into secreted lactate, which accounts for a substantial fraction of the glucose carbon utilized by the cells. Krebs- cycle activity as determined by C isotopomer distributions in glutamate, aspartate, malate and pyrimidine rings was considerably higher in the cancer cells than in the primary myocytes. Large differences were also evident in de novo biosynthesis of riboses in the free nucleotide pools, as well as entry of glucose carbon into the pyrimidine rings in the free nucleotide pool. Specific labeling patterns in these metabolites show the increased importance of anaplerotic reactions in the cancer cells to maintain the high demand for anabolic and energy metabolism compared with the slower growing primary myocytes. Serum-stimulated Rh30 cells showed higher degrees of labeling than serum starved cells, but they retained their characteristic anabolic metabolism profile. The myocytes showed evidence of de novo synthesis of glycogen, which was absent in the Rh30 cells.

ConclusionThe specific C isotopomer patterns showed that the major difference between the transformed and the primary cells is the shift from energy and maintenance metabolism in the myocytes toward increased energy and anabolic metabolism for proliferation in the Rh30 cells. The data further show that the mitochondria remain functional in Krebs- cycle activity and respiratory electron transfer that enables continued accelerated glycolysis. This may be a common adaptive strategy in cancer cells.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-7-79 contains supplementary material, which is available to authorized users.

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Autor: Teresa WM Fan - Magda Kucia - Kacper Jankowski - Richard M Higashi - Janina Ratajczak - Marius Z Ratajczak - Andrew N L

Fuente: https://link.springer.com/

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