title: Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells.
abstract: 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.
authors.affiliation: Department of Nanomedicine and Methodist Cancer Center, Methodist Hospital Research Institute, Houston, TX 77030, USA.
authors.forename: Weijia
authors.initials: W
authors.lastname: Zhang
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Kai
authors.forename: Dong Soon
authors.initials: DS
authors.lastname: Choi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Yen H
authors.initials: YH
authors.lastname: Nguyen
authors.forename: Helen
authors.initials: H
authors.lastname: Wong
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Landis
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang
authors.forename: Lidong
authors.initials: L
authors.lastname: Qin
mesh_terms: D045744:Cell Line, Tumor; D002469:Cell Separation / Q000295:instrumentation* / Q000379:methods*; D006801:Humans; D046210:Microfluidic Analytical Techniques; D014411:Neoplastic Stem Cells / Q000166:cytology*; D018874:Spheroids, Cellular / Q000166:cytology*