Oncotarget

Research Papers:

Lipid tethering of breast tumor cells enables real-time imaging of free-floating cell dynamics and drug response

Kristi R. Chakrabarti, James I. Andorko, Rebecca A. Whipple, Peipei Zhang, Elisabeth L. Sooklal, Stuart S. Martin, Christopher M. Jewell _

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Oncotarget. 2016; 7:10486-10497. https://doi.org/10.18632/oncotarget.7251

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Abstract

Kristi R. Chakrabarti1,2,3,*, James I. Andorko4,*, Rebecca A. Whipple3,5, Peipei Zhang4, Elisabeth L. Sooklal4, Stuart S. Martin2,3,5, Christopher M. Jewell3,4,6

1Medical Scientist Training Program, University of Maryland School of Medicine, Baltimore, MD 21201, USA

2Graduate Program in Molecular Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA

3Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA

4Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA

5Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA

6Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA

*These authors have contributed equally to this work

Correspondence to:

Christopher M. Jewell, e-mail: cmjewell@umd.edu, jewell.umd.edu

Keywords: circulating tumor cells, microtentacles, breast cancer, microfluidics, polyelectrolyte multilayers

Received: December 20, 2015    Accepted: January 26, 2016    Published: February 08, 2016

ABSTRACT

Free-floating tumor cells located in the blood of cancer patients, known as circulating tumor cells (CTCs), have become key targets for studying metastasis. However, effective strategies to study the free-floating behavior of tumor cells in vitro have been a major barrier limiting the understanding of the functional properties of CTCs. Upon extracellular-matrix (ECM) detachment, breast tumor cells form tubulin-based protrusions known as microtentacles (McTNs) that play a role in the aggregation and re-attachment of tumor cells to increase their metastatic efficiency. In this study, we have designed a strategy to spatially immobilize ECM-detached tumor cells while maintaining their free-floating character. We use polyelectrolyte multilayers deposited on microfluidic substrates to prevent tumor cell adhesion and the addition of lipid moieties to tether tumor cells to these surfaces through interactions with the cell membranes. This coating remains optically clear, allowing capture of high-resolution images and videos of McTNs on viable free-floating cells. In addition, we show that tethering allows for the real-time analysis of McTN dynamics on individual tumor cells and in response to tubulin-targeting drugs. The ability to image detached tumor cells can vastly enhance our understanding of CTCs under conditions that better recapitulate the microenvironments they encounter during metastasis.

Author Information

Kristi R. Chakrabarti

James I. Andorko

Rebecca A. Whipple

Peipei Zhang

Elisabeth L. Sooklal

Stuart S. Martin

Christopher M. Jewell
Primary Contact  _


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