Isolation of Phenotypically Distinct Cancer Cells Using Nanoparticle-Mediated Sorting

Brenda J. Green, Leyla Kermanshah, Mahmoud Labib, Sharif U. Ahmed, Pamuditha N. Silva, Laili Mahmoudian, I. Hsin Chang, Reza M. Mohamadi, Jonathan V. Rocheleau, Shana O. Kelley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Isolating subpopulations of heterogeneous cancer cells is an important capability for the meaningful characterization of circulating tumor cells at different stages of tumor progression and during the epithelial-to-mesenchymal transition. Here, we present a microfluidic device that can separate phenotypically distinct subpopulations of cancer cells. Magnetic nanoparticles coated with antibodies against the epithelial cell adhesion molecule (EpCAM) are used to separate breast cancer cells in the microfluidic platform. Cells are sorted into different zones on the basis of the levels of EpCAM expression, which enables the detection of cells that are losing epithelial character and becoming more mesenchymal. The phenotypic properties of the isolated cells with low and high EpCAM are then assessed using matrix-coated surfaces for collagen uptake analysis, and an NAD(P)H assay that assesses metabolic activity. We show that low-EpCAM expressing cells have higher collagen uptake and higher folate-induced NAD(P)H responses compared to those of high-EpCAM expressing cells. In addition, we tested SKBR3 cancer cells undergoing chemically induced hypoxia. The induced cells have reduced expression of EpCAM, and we find that these cells have higher collagen uptake and NAD(P)H metabolism relative to noninduced cells. This work demonstrates that nanoparticle-mediated binning facilitates the isolation of functionally distinct cell subpopulations and allows surface marker expression to be associated with invasiveness, including collagen uptake and metabolic activity.

Original languageEnglish (US)
Pages (from-to)20435-20443
Number of pages9
JournalACS Applied Materials and Interfaces
Volume9
Issue number24
DOIs
StatePublished - Jun 21 2017
Externally publishedYes

Keywords

  • breast cancer
  • epithelial-to-mesenchymal transition
  • magnetic nanoparticles
  • microfluidics
  • phenotype

ASJC Scopus subject areas

  • Materials Science(all)

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