2025Noreen Hosny '25 (Austin lab)Noreen Hosny, Kimberly Shen, Yihua Zhao, Junle Qu, Yusha Sun, George Butler, Sarah Amend, Emma U. Hammarlund, Robert Gatenby, Joel Brown, Kenneth J. Pienta, Trung V. Phan, Stephano Boyer-Paulet, Shengkai Li, Robert H. Austin, Phosphorescence-based O2 sensing reveals size-dependent survival and motility of metastatic prostate cancer cells in self-generated hypoxia, iScience, 2025, 112325, ISSN 2589-0042, https://doi.org/10.1016/j.isci.2025.112325.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, while 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.
