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Phosphorescence-based O2 sensing reveals size-dependent survival and motility of metastatic prostate cancer cells in self-generated hypoxia

Hosny, Noreen ; Shen, Kimberly ; Zhao, Yihua ; Qu, Junle ; Sun, Yusha ; Butler, George ; Amend, Sarah ; Hammarlund, Emma U. LU ; Gatenby, Robert and Brown, Joel , et al. (2025) In iScience 28(5).
Abstract

Cancer cells in solid tumors experience hypoxia, a condition of low O2 concentration, since their O2 demand exceeds the supply from the surrounding vasculature. However, how these cells adapt to hypoxia requires further elucidation. Here, we use a transparent phosphorescent thin film to visualize the self-generated hypoxia field of prostate cancer cells and quantify local O2 consumption rates, measured locally as the Laplacian of the O2 field. Single-cell tracking on steep O2 gradients revealed that larger cells exhibit higher motility and moderate migration bias toward O2-rich regions. Termination of hypoxia before cessation of O2 consumption shifted cell... (More)

Cancer cells in solid tumors experience hypoxia, a condition of low O2 concentration, since their O2 demand exceeds the supply from the surrounding vasculature. However, how these cells adapt to hypoxia requires further elucidation. Here, we use a transparent phosphorescent thin film to visualize the self-generated hypoxia field of prostate cancer cells and quantify local O2 consumption rates, measured locally as the Laplacian of the O2 field. Single-cell tracking on steep O2 gradients revealed that larger cells exhibit higher motility and moderate migration bias toward O2-rich regions. Termination of hypoxia before cessation of O2 consumption shifted cell distributions to larger sizes, whereas prolonged hypoxia induced apoptosis, producing cell populations of smaller areas post-hypoxia. Such resilience to hypoxia was absent for noncancerous fibroblasts. Our findings suggest that larger PC3 cells have enhanced metabolic fitness under hypoxia, identifying these cells as potential targets of cancer therapy.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biotechnology, Cancer, Technical aspects of cell biology
in
iScience
volume
28
issue
5
article number
112325
publisher
Elsevier
external identifiers
  • scopus:105004472356
  • pmid:40475852
ISSN
2589-0042
DOI
10.1016/j.isci.2025.112325
language
English
LU publication?
yes
id
4aa36c27-3050-4372-be9e-83878bee87de
date added to LUP
2025-08-04 12:07:46
date last changed
2025-08-18 13:18:00
@article{4aa36c27-3050-4372-be9e-83878bee87de,
  abstract     = {{<p>Cancer cells in solid tumors experience hypoxia, a condition of low O<sub>2</sub> concentration, since their O<sub>2</sub> demand exceeds the supply from the surrounding vasculature. However, how these cells adapt to hypoxia requires further elucidation. Here, we use a transparent phosphorescent thin film to visualize the self-generated hypoxia field of prostate cancer cells and quantify local O<sub>2</sub> consumption rates, measured locally as the Laplacian of the O<sub>2</sub> field. Single-cell tracking on steep O<sub>2</sub> gradients revealed that larger cells exhibit higher motility and moderate migration bias toward O<sub>2</sub>-rich regions. Termination of hypoxia before cessation of O<sub>2</sub> consumption shifted cell distributions to larger sizes, whereas prolonged hypoxia induced apoptosis, producing cell populations of smaller areas post-hypoxia. Such resilience to hypoxia was absent for noncancerous fibroblasts. Our findings suggest that larger PC3 cells have enhanced metabolic fitness under hypoxia, identifying these cells as potential targets of cancer therapy.</p>}},
  author       = {{Hosny, Noreen and Shen, Kimberly and Zhao, Yihua and Qu, Junle and Sun, Yusha and Butler, George and Amend, Sarah and Hammarlund, Emma U. and Gatenby, Robert and Brown, Joel and Pienta, Kenneth J. and Phan, Trung V. and Boyer-Paulet, Stephano and Li, Shengkai and Austin, Robert H.}},
  issn         = {{2589-0042}},
  keywords     = {{Biotechnology; Cancer; Technical aspects of cell biology}},
  language     = {{eng}},
  number       = {{5}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{Phosphorescence-based O<sub>2</sub> sensing reveals size-dependent survival and motility of metastatic prostate cancer cells in self-generated hypoxia}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2025.112325}},
  doi          = {{10.1016/j.isci.2025.112325}},
  volume       = {{28}},
  year         = {{2025}},
}