文章基本信息

标题：A persistent invasive phenotype in post-hypoxic tumor cells is revealed by fate mapping and computational modeling
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作者：Heber L. Rocha ; Inês Godet ; Furkan Kurtoglu 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：9
页码：1-23
DOI：10.1016/j.isci.2021.102935
语种：English
出版社：Elsevier
摘要：SummaryHypoxia 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.Graphical abstractDisplay OmittedHighlights•A fluorescent fate mapping system allows tracking of hypoxic and post-hypoxic cells•Computational modeling predicts the formation of post-hypoxic invasive plumes•Simulations show post-hypoxic cells must maintain persistant migration to form plumes•Tracking cells exposed to intratumoral hypoxia confirms persistent migrationCell biology; Systems biology; Cancer systems biology; Cancer