Comprehensive Metaboproteomics of Burkitt's and Diffuse Large B-Cell Lymphoma Cell Lines and Primary Tumor Tissues Reveals Distinct Differences in Pyruvate Content and Metabolism

J Proteome Res. 2017 Mar 3;16(3):1105-1120. doi: 10.1021/acs.jproteome.6b00164. Epub 2017 Feb 16.

Abstract

Burkitt's lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) are pathologically and clinically distinct subtypes of aggressive non-Hodgkin B-cell lymphoma. To learn more about their biology, we employed metabolomic and proteomic methods to study both established cell lines as well as cryopreserved and formalin-fixed paraffin-embedded (FFPE) tissue sections of BL and DLBCL. Strikingly, NMR analyses revealed DLBCL cell lines to produce and secrete significantly (padj = 1.72 × 10-22) more pyruvic acid than BL cell lines. This finding could be reproduced by targeted GC/MS analyses of cryopreserved tissue sections of BL and DLBCL cases. Enrichment analysis of an overlapping set of N = 2315 proteins, that had been quantified by nanoLC-SWATH-MS in BL and DLBCL cultured cells and cryosections, supported the observed difference in pyruvic acid content, as glycolysis and pyruvate metabolism were downregulated, while one-carbon metabolism was upregulated in BL compared to DLBCL. Furthermore, 92.1% of the overlapping significant proteins showed the same direction of regulation in cryopreserved and FFPE material. Proteome data are available via ProteomeXchange with identifier PXD004936.

Keywords: BL; DLBCL; FFPE; NMR; SWATH-MS; metabolomics; proteomics; pyruvate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Burkitt Lymphoma / metabolism*
  • Cell Line, Tumor
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / metabolism*
  • Magnetic Resonance Spectroscopy
  • Metabolomics / methods*
  • Proteomics / methods*
  • Pyruvic Acid / blood
  • Pyruvic Acid / metabolism*
  • Tumor Cells, Cultured

Substances

  • Pyruvic Acid