Hosny Noreen, Shen Kimberly, Zhao Yihua, Qu Junle, Sun Yusha, Butler George, Amend Sarah, Hammarlund Emma U, Gatenby Robert, Brown Joel, Pienta Kenneth J, Phan Trung V, Boyer-Paulet Stephano, Li Shengkai, Austin Robert H
Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
Department of Physics, Princeton University, Princeton, NJ, USA.
iScience. 2025 Apr 2;28(5):112325. doi: 10.1016/j.isci.2025.112325. eCollection 2025 May 16.
Cancer cells in solid tumors experience hypoxia, a condition of low concentration, since their 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 consumption rates, measured locally as the Laplacian of the field. Single-cell tracking on steep gradients revealed that larger cells exhibit higher motility and moderate migration bias toward -rich regions. Termination of hypoxia before cessation of 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.
实体瘤中的癌细胞会经历缺氧状态，即由于其需求超过周围脉管系统的供应而导致浓度较低的情况。然而，这些细胞如何适应缺氧仍需进一步阐明。在此，我们使用一种透明的磷光薄膜来可视化前列腺癌细胞自身产生的缺氧场，并量化局部消耗率，局部测量为该场的拉普拉斯算子。在陡峭梯度上的单细胞追踪显示，较大的细胞表现出更高的运动性以及朝向富氧区域的适度迁移偏向。在消耗停止之前终止缺氧会使细胞分布转向更大尺寸，而长时间的缺氧会诱导细胞凋亡，导致缺氧后细胞群体的面积变小。非癌性成纤维细胞则不存在这种对缺氧的适应能力。我们的研究结果表明，较大的PC3细胞在缺氧条件下具有增强的代谢适应性，将这些细胞确定为癌症治疗的潜在靶点。
