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Cancer Cell Fitness Is Dynamic.
- Source :
-
Cancer research [Cancer Res] 2021 Feb 15; Vol. 81 (4), pp. 1040-1051. Date of Electronic Publication: 2020 Dec 22. - Publication Year :
- 2021
-
Abstract
- Several phenotypes that impact the capacity of cancer cells to survive and proliferate are dynamic. Here we used the number of cells in colonies as an assessment of fitness and devised a novel method called Dynamic Fitness Analysis (DynaFit) to measure the dynamics in fitness over the course of colony formation. DynaFit is based on the variance in growth rate of a population of founder cells compared with the variance in growth rate of colonies with different sizes. DynaFit revealed that cell fitness in cancer cell lines, primary cancer cells, and fibroblasts under unhindered growth conditions is dynamic. Key cellular mechanisms such as ERK signaling and cell-cycle synchronization differed significantly among cells in colonies after 2 to 4 generations and became indistinguishable from randomly sampled cells regarding these features. In the presence of cytotoxic agents, colonies reduced their variance in growth rate when compared with their founder cell, indicating a dynamic nature in the capacity to survive and proliferate in the presence of a drug. This finding was supported by measurable differences in DNA damage and induction of senescence among cells of colonies. The presence of epigenetic modulators during the formation of colonies stabilized their fitness for at least four generations. Collectively, these results support the understanding that cancer cell fitness is dynamic and its modulation is a fundamental aspect to be considered in comprehending cancer cell biology and its response to therapeutic interventions. SIGNIFICANCE: Cancer cell fitness is dynamic over the course of the formation of colonies. This dynamic behavior is mediated by asymmetric mitosis, ERK activity, cell-cycle duration, and DNA repair capacity in the absence or presence of a drug.<br /> (©2020 American Association for Cancer Research.)
- Subjects :
- Cell Cycle drug effects
Cell Cycle physiology
Cell Proliferation drug effects
Cells, Cultured
Clone Cells pathology
Clone Cells physiology
DNA Damage drug effects
DNA Damage physiology
Genetic Fitness drug effects
Humans
MCF-7 Cells
Mitosis drug effects
Mitosis physiology
Temozolomide pharmacology
Tumor Stem Cell Assay
Cell Proliferation physiology
Genetic Fitness physiology
Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 81
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 33355182
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-20-2488