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A persistent invasive phenotype in post-hypoxic tumor cells is revealed by fate mapping and computational modeling
iScience ( IF 5.8 ) Pub Date : 2021-08-04 , DOI: 10.1016/j.isci.2021.102935
Heber L Rocha 1 , Inês Godet 2, 3 , Furkan Kurtoglu 1 , John Metzcar 1, 4 , Kali Konstantinopoulos 1 , Soumitra Bhoyar 2, 3 , Daniele M Gilkes 2, 3, 5 , Paul Macklin 1
Affiliation  

Hypoxia is a critical factor in solid tumors that has been associated with cancer progression and aggressiveness. We recently developed a hypoxia fate mapping system to trace post-hypoxic cells within a tumor for the first time. This approach uses an oxygen-dependent fluorescent switch and allowed us to measure key biological features such as oxygen distribution, cell proliferation, and migration. We developed a computational model to investigate the motility and phenotypic persistence of hypoxic and post-hypoxic cells during tumor progression. The cellular behavior was defined by phenotypic persistence time, cell movement bias, and the fraction of cells that respond to an enhanced migratory stimulus. This work combined advanced cell tracking and imaging techniques with mathematical modeling, to reveal that a persistent invasive migratory phenotype that develops under hypoxia is required for cellular escape into the surrounding tissue, promoting the formation of invasive structures (“plumes”) that expand toward the oxygenated tumor regions.



中文翻译:

命运图谱和计算模型揭示了缺氧后肿瘤细胞的持续侵袭性表型

缺氧是实体瘤中的一个关键因素,与癌症进展和侵袭性有关。我们最近开发了一种缺氧命运映射系统,首次追踪肿瘤内的缺氧后细胞。这种方法使用氧依赖性荧光开关,使我们能够测量关键的生物学特征,如氧分布、细胞增殖和迁移。我们开发了一个计算模型来研究肿瘤进展过程中缺氧和缺氧后细胞的运动性和表型持续性。细胞行为由表型持续时间、细胞运动偏差和对增强的迁移刺激作出反应的细胞比例定义。这项工作将先进的细胞跟踪和成像技术与数学建模相结合,

更新日期:2021-09-16
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