Rhabdomyosarcoma cells show an energy producing anabolic metabolic phenotype compared with primary myocytes

Teresa W.M. Fan, Magda Kucia, Kacper Jankowski, Richard M. Higashi, Janina Ratajczak, Marius Z. Ratajczak, Andrew N. Lane

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Background: The 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 13C-labeled glucose was used as a source molecule to follow the incorporation of 13C 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. Results: The 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 13C 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. Conclusion: The specific 13C 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.

Original languageEnglish
Article number79
JournalMolecular Cancer
Volume7
DOIs
StatePublished - Oct 21 2008

Bibliographical note

Funding Information:
This work was supported by the Brown Foundation, Kentucky Challenge for Excellence (to ANL), NIH Grant RR018733 from the National Center for Research Resources, National Cancer Institute Grants 1 R01CA101199-01 and 1R01CA118434-01A2 to TWMF, NIH R01 CA106281-01 to MZR, NSF EPSCoR grant EPS-0132295 for the 18.8 T NMR spectrometer, and EPSCoR grant EPS-0447479 to TWMF for the development of isotopomer-based metabolomic analysis.

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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