A physical sciences network characterization of circulating tumor cell aggregate transport

Michael R. King, Kevin G. Phillips, Annachiara Mitrugno, Tae Rin Lee, Adelaide M.E. de Guillebon, Siddarth Chandrasekaran, Matthew J. McGuire, Russell T. Carr, Sandra M. Baker-Groberg, Rachel A. Rigg, Anand Kolatkar, Madelyn Luttgen, Kelly Bethel, Peter Kuhn, Paolo Decuzzi, Owen J.T. McCarty

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Circulating tumor cells (CTC) have been implicated in the hematogenous spread of cancer. To investigate the fluid phase of cancer from a physical sciences perspective, the multi-institutional Physical Sciences-Oncology Center (PS-OC) Network performed multidisciplinary biophysical studies of single CTC and CTC aggregates from a patient with breast cancer. CTCs, ranging from single cells to aggregates comprised of 2–5 cells, were isolated using the high-definition CTC assay and biophysically profiled using quantitative phase microscopy. Single CTCs and aggregates were then modeled in an in vitro system comprised of multiple breast cancer cell lines and microfluidic devices used to model E-selectin mediated rolling in the vasculature. Using a numerical model coupling elastic collisions between red blood cells and CTCs, the dependence of CTC vascular margination on single CTCs and CTC aggregate morphology and stiffness was interrogated. These results provide a multifaceted characterization of single CTC and CTC aggregate dynamics in the vasculature and illustrate a framework to integrate clinical, biophysical, and mathematical approaches to enhance our understanding of the fluid phase of cancer.

Original languageEnglish (US)
Pages (from-to)C792-C802
JournalAmerican Journal of Physiology - Cell Physiology
Volume308
Issue number10
DOIs
StatePublished - May 15 2015

Keywords

  • Breast cancer
  • Cell lines
  • Circulating tumor cell
  • Fluid dynamics
  • Hemodynamics
  • Immersed finite element method
  • Metastasis
  • Microfluidics
  • Physics of cancer
  • Quantitative phase microscopy

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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  • Cite this

    King, M. R., Phillips, K. G., Mitrugno, A., Lee, T. R., de Guillebon, A. M. E., Chandrasekaran, S., McGuire, M. J., Carr, R. T., Baker-Groberg, S. M., Rigg, R. A., Kolatkar, A., Luttgen, M., Bethel, K., Kuhn, P., Decuzzi, P., & McCarty, O. J. T. (2015). A physical sciences network characterization of circulating tumor cell aggregate transport. American Journal of Physiology - Cell Physiology, 308(10), C792-C802. https://doi.org/10.1152/ajpcell.00346.2014