Tumor Heterogeneity Shapes Survival Dynamics in Drug-Treated Cells, Revealing Size-Drifting Subpopulations
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Le résumé fourni par la source
The goal of this project was to demonstrate that subpopulations of cells in tumors can uniquely fluctuate in size in response to environmental conditions created during drug treatment, thereby acting as a dynamic “rheostat” to create a favorable tumor environment for growth. The cancer modeling used for these studies was subpopulations of melanoma cells existing in cultured and tumor systems that differed in aldehyde dehydrogenase (ALDH) activity. However, similar observations were found in other cancer types in addition to melanoma, making them applicable broadly across cancer. The approach was designed to show that either ALDH high and ALDH low subpopulations rapidly epigenetically transition between stem-cell-like high into nonstem-like low production states to create an environment during drug treatment that would enable optimal cellular proliferation and tumor expansion to facilitate drug resistance. The controlled experiments showed proportional changes in each cell population to reach an evolutionarily stable equilibrium mediated by the needed levels of ALDH enzyme activity. Mechanistically, cell population size changes served to functionally move the aldehyde and the resulting reactive oxygen species (ROS) levels to those compatible with optimal cellular proliferation with population fluctuations dependent on the levels of drug induced tumor stress. This is the first report documenting fluctuations in the sizes of cell populations in tumors to cooperatively assist in drug resistance development.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Tumor Heterogeneity Shapes Survival Dynamics in Drug-Treated Cells, Revealing Size-Drifting Subpopulations
- Date Crossref
- 17/10/2024
- Éditeur
- American Chemical Society (ACS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Pennsylvania State University Department of Pharmacology pays non établi dans la noticeUniversité ou école supérieure
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The Wistar Institute pays non établi dans la noticeStructure de recherche
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Washington State University Spokane pays non établi dans la noticeUniversité ou école supérieure
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Molecular and Cellular Oncogenesis Program and Melanoma Research Center pays non établi dans la noticeStructure de recherche
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Washington State University College of Pharmacy and Pharmaceutical Sciences Department of Pharmaceutical Sciences pays non établi dans la noticeUniversité ou école supérieure
Department of Pharmacology — Pennsylvania State University, The Wistar Institute et Washington State University Spokane, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.