Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells

作者：Zhang Weijia; Kai Kazuharu; Choi Dong Soon; Iwamoto Takayuki; Nguyen Yen H; Wong Helen; Landis Melissa D; Ueno Naoto T^*; Chang Jenny; Qin Lidong

来源：Proceedings of the National Academy of Sciences, 2012, 109(46): 18707-18712.

DOI：10.1073/pnas.1209893109

• cell mechanics
• cytoskeleton
• genomic profiling

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.

• 出版日期2012-11-13