Tables S1-5, Figures S1-S6, 3 Methods from Identification of a Human Airway Epithelial Cell Subpopulation with Altered Biophysical, Molecular, and Metastatic Properties
journal contribution
posted on 2023-04-03, 22:05 authored by Paul C. Pagano, Linh M. Tran, Nawal Bendris, Sean O'Byrne, Henry T. Tse, Shivani Sharma, Jonathan W. Hoech, Stacy J. Park, Elvira L. Liclican, Zhe Jing, Rui Li, Kostyantyn Krysan, Manash K. Paul, Yari Fontebasso, Jill E. Larsen, Shaina Hakimi, Atsuko Seki, Michael C. Fishbein, James K. Gimzewski, Dino Di Carlo, John D. Minna, Tonya C. Walser, Steven M. DubinettSupplemental Tables, Figures, and Methods
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National Center for Advancing Translational Sciences
University of California Tobacco-Related Disease Research Program
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ARTICLE ABSTRACT
Lung cancers are documented to have remarkable intratumoral genetic heterogeneity. However, little is known about the heterogeneity of biophysical properties, such as cell motility, and its relationship to early disease pathogenesis and micrometastatic dissemination. In this study, we identified and selected a subpopulation of highly migratory premalignant airway epithelial cells that were observed to migrate through microscale constrictions at up to 100-fold the rate of the unselected immortalized epithelial cell lines. This enhanced migratory capacity was found to be Rac1-dependent and heritable, as evidenced by maintenance of the phenotype through multiple cell divisions continuing more than 8 weeks after selection. The morphology of this lung epithelial subpopulation was characterized by increased cell protrusion intensity. In a murine model of micrometastatic seeding and pulmonary colonization, the motility-selected premalignant cells exhibit both enhanced survival in short-term assays and enhanced outgrowth of premalignant lesions in longer-term assays, thus overcoming important aspects of “metastatic inefficiency.” Overall, our findings indicate that among immortalized premalignant airway epithelial cell lines, subpopulations with heritable motility-related biophysical properties exist, and these may explain micrometastatic seeding occurring early in the pathogenesis of lung cancer. Understanding, targeting, and preventing these critical biophysical traits and their underlying molecular mechanisms may provide a new approach to prevent metastatic behavior. Cancer Prev Res; 10(9); 514–24. ©2017 AACR.See related editorial by Hynds and Janes, p. 491Usage metrics
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Keywords
Biological Agents & TherapiesGene therapyBiomarkersCancer PreventionBiological mechanisms in preventionPersonalized cancer preventionCarcinogenesisAnimal models of carcinogenesisPremalignancyCell SignalingComputational MethodsGene expression profilingLung CancerProgression, Invasion & MetastasisMigration and invasion
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