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Fate-mapping post-hypoxic tumor cells reveals a ROS-resistant phenotype that promotes metastasis

Author

Listed:
  • Inês Godet

    (The Johns Hopkins University School of Medicine
    The Johns Hopkins University)

  • Yu Jung Shin

    (The Johns Hopkins University School of Medicine)

  • Julia A. Ju

    (The Johns Hopkins University School of Medicine
    The Johns Hopkins University)

  • I Chae Ye

    (The Johns Hopkins University School of Medicine)

  • Guannan Wang

    (The Johns Hopkins University School of Medicine)

  • Daniele M. Gilkes

    (The Johns Hopkins University School of Medicine
    The Johns Hopkins University
    The Johns Hopkins University School of Medicine)

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 O2 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.’

Suggested Citation

  • Inês Godet & Yu Jung Shin & Julia A. Ju & I Chae Ye & Guannan Wang & Daniele M. Gilkes, 2019. "Fate-mapping post-hypoxic tumor cells reveals a ROS-resistant phenotype that promotes metastasis," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12412-1
    DOI: 10.1038/s41467-019-12412-1
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    Cited by:

    1. Silje Kjølle & Kenneth Finne & Even Birkeland & Vandana Ardawatia & Ingeborg Winge & Sura Aziz & Gøril Knutsvik & Elisabeth Wik & Joao A. Paulo & Heidrun Vethe & Dimitrios Kleftogiannis & Lars A. Aksl, 2023. "Hypoxia induced responses are reflected in the stromal proteome of breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Inês Godet & Harsh H. Oza & Yi Shi & Natalie S. Joe & Alyssa G. Weinstein & Jeanette Johnson & Michael Considine & Swathi Talluri & Jingyuan Zhang & Reid Xu & Steven Doctorman & Delma Mbulaiteye & Gen, 2024. "Hypoxia induces ROS-resistant memory upon reoxygenation in vivo promoting metastasis in part via MUC1-C," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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