title: Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma are highly dependent on oxidative phosphorylation.
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.
authors.affiliation: Dr. Senckenberg Institute of Pathology, Goethe-University Hospital, Theodor-Stern-Kai 7, Frankfurt Am Main, 60596, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Birkenmeier
authors.affiliation: Clinic of Anesthesiology, Intensive-Care Medicine and Pain Therapy, Goethe-University Hospital, Theodor-Stern Kai 7, Frankfurt Am Main, 60596, Germany.|Centre of Biological Chemistry, and Centre for Membrane Proteomics, Molecular Bioenergetics Group, Medical School, Goethe-University, Theodor-Stern-Kai 7, Frankfurt Am Main, 60596, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Dröse
authors.affiliation: Centre of Biological Chemistry, and Centre for Membrane Proteomics, Molecular Bioenergetics Group, Medical School, Goethe-University, Theodor-Stern-Kai 7, Frankfurt Am Main, 60596, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Wittig
authors.affiliation: Dr. Senckenberg Institute of Pathology, Goethe-University Hospital, Theodor-Stern-Kai 7, Frankfurt Am Main, 60596, Germany.
authors.forename: Ria
authors.initials: R
authors.lastname: Winkelmann
authors.affiliation: Dr. Senckenberg Institute of Pathology, Goethe-University Hospital, Theodor-Stern-Kai 7, Frankfurt Am Main, 60596, Germany.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Käfer
authors.affiliation: Dr. Senckenberg Institute of Pathology, Goethe-University Hospital, Theodor-Stern-Kai 7, Frankfurt Am Main, 60596, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Döring
authors.affiliation: Dr. Senckenberg Institute of Pathology, Goethe-University Hospital, Theodor-Stern-Kai 7, Frankfurt Am Main, 60596, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hartmann
authors.affiliation: Institute for Genetics, University of Cologne, Zülpicher Str. 47A, Cologne, 50674, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Wenz
authors.affiliation: Institute of Biochemistry and Molecular Biology I, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Reichert
authors.affiliation: Department of Pediatrics, Radboud University Medical Center, Nijmegen Center for Mitochondrial Disorders (NCMD), The Netherlands.|Cluster of Excellence Frankfurt "Macromolecular Complexes", Goethe-University, Frankfurt Am Main, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Brandt
authors.affiliation: Dr. Senckenberg Institute of Pathology, Goethe-University Hospital, Theodor-Stern-Kai 7, Frankfurt Am Main, 60596, Germany.
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
mesh_terms: D015153:Blotting, Western; D005434:Flow Cytometry; D006689:Hodgkin Disease / Q000378:metabolism*; D006801:Humans; D010085:Oxidative Phosphorylation; D016539:Reed-Sternberg Cells / Q000378:metabolism*
keywords: classical Hodgkin lymphoma; energy metabolism; oxidative phosphorylation