Nanoparticle-based sorting of circulating tumor cells by epithelial antigen expression during disease progression in an animal model

Nidal Muhanna, Adam Mepham, Reza M. Mohamadi, Harley Chan, Tahsin Khan, Margarete Akens, Justin D. Besant, Jonathan Irish*, Shana O. Kelley

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Circulating tumor cells (CTCs) can be used as markers for the detection, characterization, and targeted therapeutic management of cancer. We recently developed a nanoparticle-mediated approach for capture and sorting of CTCs based on their specific epithelial phenotype. In the current study, we investigate the phenotypic transition of tumor cells in an animal model and show the correlation of this transition with tumor progression. VX2 tumor cells were injected into rabbits, and CTCs were evaluated during tumor progression and correlated with computerized tomography (CT) measurements of tumor volume. The results showed a dramatic increase of CTCs during the four weeks of tumor growth. Following resection, CTC levels dropped but then rebounded, likely due to lymph node metastases. Additionally, CTCs showed a marked loss of the epithelial cell adhesion molecule (EpCAM) relative to precursor cells. In conclusion, the device accurately traces disease progression and CTC phenotypic shift in an animal model. From the Clinical Editor: The detection of circulating tumor cells (CTCs) has been used to predict disease prognosis. In this study, the authors developed a nanoparticle-mediated platform based on microfluidics to analyze the differential expressions of epithelial cell adhesion molecule (EpCAM) on CTCs in an animal model. It was found that the loss of EpCAM correlated with disease progression. Hence, the use of this platform may be further applied in other cancer models in the future.

Original languageEnglish
Pages (from-to)1613-1620
Number of pages8
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume11
Issue number7
DOIs
StatePublished - 1 Oct 2015
Externally publishedYes

Funding

FundersFunder number
CMC Microsystems
Ontario Research Foundation
Canadian Cancer Society Research Institute
Canadian Institutes of Health Research
Natural Sciences and Engineering Research Council of Canada

    Keywords

    • Cell sorting
    • Circulating tumor cells
    • Microfluidics
    • Nanoparticle
    • Rabbit cancer model

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