Journal
ISCIENCE
Volume 24, Issue 9, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2021.102935
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Funding
- NCI [U01-CA232137, U54CA210173]
- NSF [1720625, 1818187]
- Breast Cancer Research Foundation
- Jayne Koskinas Ted Giovanis Foundation for Health and Policy
- Susan G. Komen Foundation [CCR17483484]
- Cindy Rosencrans Fund for Metastatic Triple-Negative Breast Cancer
- Emerson Collective
- SKCCC Core Grant (NCI) [P50CA006973]
- Lilly Endowment, Inc.
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1818187] Funding Source: National Science Foundation
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Hypoxia plays a critical role in solid tumor progression and aggressiveness. A new hypoxia fate mapping system allows for the tracking of post-hypoxic cells within tumors. Computational modeling was used to investigate the motility and phenotypic persistence of hypoxic and post-hypoxic cells during tumor progression.
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 tomeasure 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.
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