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.
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.
Philipp
P
Schwarzfischer
Jörg
J
Reinders
Katja
K
Dettmer
Institute of Pathology, Charité-University Medicine Berlin , Campus Benjamin Franklin, 10117 Berlin, Germany.
Karsten
K
Kleo
Institute of Pathology, Charité-University Medicine Berlin , Campus Benjamin Franklin, 10117 Berlin, Germany.
Lora
L
Dimitrova
Institute of Pathology, Charité-University Medicine Berlin , Campus Benjamin Franklin, 10117 Berlin, Germany.
Michael
M
Hummel
Department of Hematology and Oncology, University Medical Center Goettingen , 37073 Goettingen, Germany.
Maren
M
Feist
Department of Hematology and Oncology, University Medical Center Goettingen , 37073 Goettingen, Germany.
Dieter
D
Kube
Institute of Hematopathology, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel , 24118 Kiel, Germany.
Monika
M
Szczepanowski
Institute of Hematopathology, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel , 24118 Kiel, Germany.
Wolfram
W
Klapper
Franziska
F
Taruttis
Julia C
JC
Engelmann
Rainer
R
Spang
Wolfram
0000-0003-3646-0060
W
Gronwald
Peter J
PJ
Oefner
D002051:Burkitt Lymphoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics / Q000379:methods*; D040901:Proteomics / Q000379:methods*; D019289:Pyruvic Acid / Q000097:blood / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D019289:Pyruvic Acid
BL; DLBCL; FFPE; NMR; SWATH-MS; metabolomics; proteomics; pyruvate