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Plasma redox imbalance caused by albumin oxidation promotes lung-predominant NETosis and pulmonary cancer metastasis

Author

Listed:
  • Minoru Inoue

    (University Health Network)

  • Ryota Nakashima

    (University Health Network)

  • Masahiro Enomoto

    (University Health Network)

  • Yuhki Koike

    (Mie University Graduate School of Medicine)

  • Xiao Zhao

    (University Health Network)

  • Kenneth Yip

    (University Health Network)

  • Shao Hui Huang

    (University Healthy Network
    University of Toronto)

  • John N. Waldron

    (University Healthy Network
    University of Toronto)

  • Mitsuhiko Ikura

    (University Health Network
    University of Toronto)

  • Fei-Fei Liu

    (University Health Network
    University Healthy Network
    University of Toronto
    University of Toronto)

  • Scott V. Bratman

    (University Health Network
    University Healthy Network
    University of Toronto
    University of Toronto)

Abstract

Neutrophil extracellular traps (NETs) promote cancer metastasis in preclinical models following massive exogenous inflammatory stimuli. It remains unknown whether cancer hosts under physiologic conditions experience NETosis and consequent metastasis. Here we show that plasma redox imbalance caused by albumin oxidation promotes inflammation-independent NETosis. Albumin is the major source of free thiol that maintains redox balance. Oxidation of albumin-derived free thiol is sufficient to trigger NETosis via accumulation of reactive oxygen species within neutrophils. The resultant NETs are found predominantly within lungs where they contribute to the colonization of circulating tumor cells leading to pulmonary metastases. These effects are abrogated by pharmacologic inhibition of NET formation. Moreover, albumin oxidation is associated with pulmonary metastasis in a cohort of head and neck cancer patients. These results implicate plasma redox balance as an endogenous and physiologic regulator of NETosis and pulmonary cancer metastasis, providing new therapeutic and diagnostic opportunities for combatting cancer progression.

Suggested Citation

  • Minoru Inoue & Ryota Nakashima & Masahiro Enomoto & Yuhki Koike & Xiao Zhao & Kenneth Yip & Shao Hui Huang & John N. Waldron & Mitsuhiko Ikura & Fei-Fei Liu & Scott V. Bratman, 2018. "Plasma redox imbalance caused by albumin oxidation promotes lung-predominant NETosis and pulmonary cancer metastasis," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07550-x
    DOI: 10.1038/s41467-018-07550-x
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