Peripheral blood mononuclear cells exhibit increased mitochondrial respiration after adjuvant chemo- and radiotherapy for early breast cancer
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Peripheral blood mononuclear cells exhibit increased mitochondrial respiration after adjuvant chemo- and radiotherapy for early breast cancer. / Christensen, Ida Bager; Abrahamsen, Marie Louise; Ribas, Lucas; Buch-Larsen, Kristian; Marina, Djordje; Andersson, Michael; Larsen, Steen; Schwarz, Peter; Dela, Flemming; Gillberg, Linn.
In: Cancer Medicine, Vol. 12, No. 16, 2023, p. 16985-16996.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Peripheral blood mononuclear cells exhibit increased mitochondrial respiration after adjuvant chemo- and radiotherapy for early breast cancer
AU - Christensen, Ida Bager
AU - Abrahamsen, Marie Louise
AU - Ribas, Lucas
AU - Buch-Larsen, Kristian
AU - Marina, Djordje
AU - Andersson, Michael
AU - Larsen, Steen
AU - Schwarz, Peter
AU - Dela, Flemming
AU - Gillberg, Linn
N1 - Publisher Copyright: © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2023
Y1 - 2023
N2 - Background: Adjuvant chemo- and radiotherapy cause cellular damage to tumorous and healthy dividing cells. Chemotherapy has been shown to cause mitochondrial respiratory dysfunction in non-tumorous tissues, but the effects on human peripheral blood mononuclear cells (PBMCs) remain unknown. Aim: We aimed to investigate mitochondrial respiration of PBMCs before and after adjuvant chemo- and radiotherapy in postmenopausal patients with early breast cancer (EBC) and relate these to metabolic parameters of the patients. Methods: Twenty-three postmenopausal women diagnosed with EBC were examined before and shortly after chemotherapy with (n = 18) or without (n = 5) radiotherapy. Respiration (O2 flux per million PBMCs) was assessed by high-resolution respirometry of intact and permeabilized PBMCs. Clinical metabolic characteristics and mitochondrial DNA (mtDNA) content of PBMCs (mtDN relative to nuclear DNA) were furthermore assessed. Results: Respiration of intact and permeabilized PBMCs from EBC patients significantly increased with adjuvant chemo- and radiotherapy (p = 6 × 10−5 and p = 1 × 10−7, respectively). The oxygen flux attributed to specific mitochondrial complexes and respiratory states increased by 17–43% compared to before therapy initiation. Similarly, PBMC mtDNA content increased by 40% (p = 0.002). Leukocytes (p = 0.0001), hemoglobin (p = 0.0003), and HDL cholesterol (p = 0.003) concentrations decreased whereas triglyceride (p = 0.01) and LDL (p = 0.02) concentrations increased after treatment suggesting a worsened metabolic state. None of the metabolic parameters or the mtDNA content of PBMCs correlated significantly with PBMC respiration. Conclusion: This study shows that mitochondrial respiration and mtDNA content in circulating PBMCs increase after adjuvant chemo- and radiotherapy in postmenopausal patients with EBC. Besides the increased mtDNA content, a shift in PBMC subpopulation proportions towards cells relying on oxidative phosphorylation, who may be less sensitive to chemotherapy, might influence the increased mitochondrial respiration observed iafter chemotherapy.
AB - Background: Adjuvant chemo- and radiotherapy cause cellular damage to tumorous and healthy dividing cells. Chemotherapy has been shown to cause mitochondrial respiratory dysfunction in non-tumorous tissues, but the effects on human peripheral blood mononuclear cells (PBMCs) remain unknown. Aim: We aimed to investigate mitochondrial respiration of PBMCs before and after adjuvant chemo- and radiotherapy in postmenopausal patients with early breast cancer (EBC) and relate these to metabolic parameters of the patients. Methods: Twenty-three postmenopausal women diagnosed with EBC were examined before and shortly after chemotherapy with (n = 18) or without (n = 5) radiotherapy. Respiration (O2 flux per million PBMCs) was assessed by high-resolution respirometry of intact and permeabilized PBMCs. Clinical metabolic characteristics and mitochondrial DNA (mtDNA) content of PBMCs (mtDN relative to nuclear DNA) were furthermore assessed. Results: Respiration of intact and permeabilized PBMCs from EBC patients significantly increased with adjuvant chemo- and radiotherapy (p = 6 × 10−5 and p = 1 × 10−7, respectively). The oxygen flux attributed to specific mitochondrial complexes and respiratory states increased by 17–43% compared to before therapy initiation. Similarly, PBMC mtDNA content increased by 40% (p = 0.002). Leukocytes (p = 0.0001), hemoglobin (p = 0.0003), and HDL cholesterol (p = 0.003) concentrations decreased whereas triglyceride (p = 0.01) and LDL (p = 0.02) concentrations increased after treatment suggesting a worsened metabolic state. None of the metabolic parameters or the mtDNA content of PBMCs correlated significantly with PBMC respiration. Conclusion: This study shows that mitochondrial respiration and mtDNA content in circulating PBMCs increase after adjuvant chemo- and radiotherapy in postmenopausal patients with EBC. Besides the increased mtDNA content, a shift in PBMC subpopulation proportions towards cells relying on oxidative phosphorylation, who may be less sensitive to chemotherapy, might influence the increased mitochondrial respiration observed iafter chemotherapy.
KW - breast cancer
KW - chemotherapy
KW - energy metabolism
KW - high-resolution respirometry
KW - mitochondria
KW - peripheral blood mononuclear cells
U2 - 10.1002/cam4.6333
DO - 10.1002/cam4.6333
M3 - Journal article
C2 - 37439084
AN - SCOPUS:85165196801
VL - 12
SP - 16985
EP - 16996
JO - Cancer Medicine
JF - Cancer Medicine
SN - 2045-7634
IS - 16
ER -
ID: 362064604