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Hodgkin and R eed– S ternberg cells of classical H odgkin lymphoma are highly dependent on oxidative phosphorylation
Author(s) -
Birkenmeier Katrin,
Dröse Stefan,
Wittig Ilka,
Winkelmann Ria,
Käfer Viktoria,
Döring Claudia,
Hartmann Sylvia,
Wenz Tina,
Reichert Andreas S.,
Brandt Ulrich,
Hansmann MartinLeo
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29934
Subject(s) - oxidative phosphorylation , cell culture , mitochondrion , lymphoma , mitochondrial biogenesis , cancer research , biology , germinal center , cell growth , chemistry , b cell , biochemistry , immunology , genetics , antibody
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.