Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 46, Pages 18707-18712Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1209893109
Keywords
cell mechanics; cytoskeleton; genomic profiling
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Funding
- Cancer Prevention and Research Institute of Texas [CPRIT-R1007]
- Emily Herman Research Fund
- Golfers Against Cancer Foundation
- State of Texas Rare and Aggressive Breast Cancer Research Program
- [U54-CA149196]
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Here we report a microfluidics method to enrich physically deformable cells by mechanical manipulation through artificial microbarriers. Driven by hydrodynamic forces, flexible cells or cells with high metastatic propensity change shape to pass through the microbarriers and exit the separation device, whereas stiff cells remain trapped. We demonstrate the separation of (i) a mixture of two breast cancer cell types (MDA-MB-436 and MCF-7) with distinct deformabilities and metastatic potentials, and (ii) a heterogeneous breast cancer cell line (SUM149), into enriched flexible and stiff subpopulations. We show that the flexible phenotype is associated with overexpression of multiple genes involved in cancer cell motility and metastasis, and greater mammosphere formation efficiency. Our observations support the relationship between tumor-initiating capacity and cell deformability, and demonstrate that tumor-initiating cells are less differentiated in terms of cell biomechanics.
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