Fate-mapping post-hypoxic tumor cells reveals a ROS-resistant phenotype that promotes metastasis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31649238.
- Also identified by DOI 10.1038/s41467-019-12412-1 and PMC identifier 6813355.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Hypoxia is known to be detrimental in cancer and contributes to its development. In this work, we present an approach to fate-map hypoxic cells in vivo in order to determine their cellular response to physiological O<sub>2</sub> gradients as well as to quantify their contribution to metastatic spread. We demonstrate the ability of the system to fate-map hypoxic cells in 2D, and in 3D spheroids and organoids. We identify distinct gene expression patterns in cells that experienced intratumoral hypoxia in vivo compared to cells exposed to hypoxia in vitro. The intratumoral hypoxia gene-signature is a better prognostic indicator for distant metastasis-free survival. Post-hypoxic tumor cells have an ROS-resistant phenotype that provides a survival advantage in the bloodstream and promotes their ability to establish overt metastasis. Post-hypoxic cells retain an increase in the expression of a subset of hypoxia-inducible genes at the metastatic site, suggesting the possibility of a 'hypoxic memory.'
Medical subject headings
- Reactive Oxygen Species
- Spheroids, Cellular
- Transcriptome
- Tumor Hypoxia