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

Weijia Zhang, Kazuharu Kai, Dong Soon Choi, Takayuki Iwamoto, Yen H. Nguyen, Helen Wong, Melissa D. Landis, Naoto T. Ueno, Jenny Chang, Lidong Qin

Research output: Contribution to journalArticle

119 Citations (Scopus)

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 associatedwith overexpression of multiple genes involved in cancer cellmotility 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.

Original languageEnglish
Pages (from-to)18707-18712
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number46
DOIs
Publication statusPublished - Nov 13 2012
Externally publishedYes

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Microfluidics
Neoplastic Stem Cells
Stem Cells
Breast Neoplasms
Hydrodynamics
Biomechanical Phenomena
Neoplasm Metastasis
Phenotype
Cell Line
Equipment and Supplies
Genes
Neoplasms

Keywords

  • Cell mechanics
  • Cytoskeleton
  • Genomic profiling

ASJC Scopus subject areas

  • General

Cite this

Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells. / Zhang, Weijia; Kai, Kazuharu; Choi, Dong Soon; Iwamoto, Takayuki; Nguyen, Yen H.; Wong, Helen; Landis, Melissa D.; Ueno, Naoto T.; Chang, Jenny; Qin, Lidong.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 46, 13.11.2012, p. 18707-18712.

Research output: Contribution to journalArticle

Zhang, Weijia ; Kai, Kazuharu ; Choi, Dong Soon ; Iwamoto, Takayuki ; Nguyen, Yen H. ; Wong, Helen ; Landis, Melissa D. ; Ueno, Naoto T. ; Chang, Jenny ; Qin, Lidong. / Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 46. pp. 18707-18712.
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