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

Minoru Inoue, Ryota Nakashima, Masahiro Enomoto, Yuhki Koike, Xiao Zhao, Kenneth Yip, Shao Hui Huang, John N. Waldron, Mitsuhiko Ikura, Fei-Fei Liu and Scott V. Bratman ()
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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
John N. Waldron: University Healthy Network
Mitsuhiko Ikura: University Health Network
Fei-Fei Liu: University Health Network
Scott V. Bratman: University Health Network

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07550-x

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