Hodgkin and Reed–Sternberg cells of classical Hodgkin lymphoma are highly dependent on oxidative phosphorylation |
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| Authors: | Katrin Birkenmeier Stefan Dröse Ilka Wittig Ria Winkelmann Viktoria Käfer Claudia Döring Sylvia Hartmann Tina Wenz Andreas S. Reichert Ulrich Brandt Martin‐Leo Hansmann |
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| Affiliation: | 1. Dr. Senckenberg Institute of Pathology, Goethe‐University Hospital, Frankfurt Am Main, Germany;2. Clinic of Anesthesiology, Intensive‐Care Medicine and Pain Therapy, Goethe‐University Hospital, Frankfurt Am Main, Germany;3. Centre of Biological Chemistry, and Centre for Membrane Proteomics, Molecular Bioenergetics Group, Medical School, Goethe‐University, Frankfurt Am Main, Germany;4. Institute for Genetics, University of Cologne, Cologne, Germany;5. Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich‐Heine‐University, Düsseldorf, Germany;6. Department of Pediatrics, Radboud University Medical Center, Nijmegen Center for Mitochondrial Disorders (NCMD), The Netherlands;7. Cluster of Excellence Frankfurt “Macromolecular Complexes”, Goethe‐University, Frankfurt Am Main, Germany |
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| Abstract: | The metabolic properties of lymphomas derived from germinal center (GC) B cells have important implications for therapeutic strategies. In this study, we have compared metabolic features of Hodgkin–Reed–Sternberg (HRS) cells, the tumor cells of classical Hodgkin's lymphoma (cHL), one of the most frequent (post‐)GC‐derived B‐cell lymphomas, with their normal GC B cell counterparts. We found that the ratio of oxidative to nonoxidative energy conversion was clearly shifted toward oxidative phosphorylation (OXPHOS)‐linked ATP synthesis in HRS cells as compared to GC B cells. Mitochondrial mass, the expression of numerous key proteins of oxidative metabolism and markers of mitochondrial biogenesis were markedly upregulated in cHL cell lines and in primary cHL cases. NFkappaB promoted this shift to OXPHOS. Functional analysis indicated that both cell growth and viability of HRS cells depended on OXPHOS. The high rates of OXPHOS correlated with an almost complete lack of lactate production in HRS cells not observed in other GC B‐cell lymphoma cell lines. Overall, we conclude that OXPHOS dominates energy conversion in HRS cells, while nonoxidative ATP production plays a subordinate role. Our results suggest that OXPHOS could be a new therapeutic target and may provide an avenue toward new treatment strategies in cHL. |
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| Keywords: | classical Hodgkin lymphoma energy metabolism oxidative phosphorylation |
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