Abstract
The lack of knowledge about the effect of inspiratory hyperoxia (IH) on the lung-specific tumor microenvironment and progression of lung cancer has attracted considerable attention. This study proposes that IH has special significance for the malignant phenotype of lung cancer cells. The effects of different oxygenation parameters on the proliferation, apoptosis, invasion and migration of lung cancer cells were systematically evaluated in vitro and in vivo. Our results reveal that IH treatment (60% O2, 6 h·day−1) not only has no tumor progression-promoting effects, but also suppresses lung cancer metastasis and promotes long-term survival. We also combined transcriptome, proteome and metabolome analysis and found that hyperoxia treatment induced significant intracellular metabolic changes in lung cancer cells. Overall, we established that MYC/SLC1A5-induced metabolic reprogramming and glutamine addiction is a new mechanism that drives lung cancer metastasis, which can be significantly suppressed by IH treatment. These findings are relevant to the debate on the perils, promises and antitumor effect of IH, especially for patients with lung cancer.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: The authors declare that they have no competing interests.
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- Received January 11, 2022.
- Accepted May 18, 2022.
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