Development of coagulation factor probes for the identification of procoagulant circulating tumor cells

Garth W. Tormoen, Flor A. Cianchetti, Paul E. Bock, Owen McCarty

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Metastatic cancer is associated with a hypercoagulable state, and pathological venous thromboembolic disease is a significant source of morbidity and the second leading cause of death in patients with cancer. Here we aimed to develop a novel labeling strategy to detect and quantify procoagulant circulating tumor cells (CTCs) from patients with metastatic cancer. We hypothesize that the enumeration of procoagulant CTCs may be prognostic for the development of venous thrombosis in patients with cancer. Our approach is based on the observation that cancer cells are capable of initiating and facilitating cell-mediated coagulation in vitro, whereby activated coagulation factor complexes assemble upon cancer cell membrane surfaces. Binding of fluorescently labeled, active site-inhibited coagulation factors VIIa, Xa, and IIa to the metastatic breast cancer cell line, MDA-MB-231, non-metastatic colorectal cell line, SW480, or metastatic colorectal cell line, SW620, was characterized in a purified system, in anticoagulated blood and plasma, and in plasma under conditions of coagulation. We conclude that a CTC labeling strategy that utilizes coagulation factor-based fluorescent probes may provide a functional assessment of the procoagulant potential of CTCs, and that this strategy is amenable to current CTC detection platforms.

Original languageEnglish (US)
Article numberArticle 110
JournalFrontiers in Oncology
Volume2 SEP
DOIs
StatePublished - 2012

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Circulating Neoplastic Cells
Blood Coagulation Factors
Neoplasms
Cell Line
Factor VIIa
Factor Xa
Fluorescent Dyes
Venous Thrombosis
Cause of Death
Catalytic Domain
Cell Membrane
Breast Neoplasms
Morbidity

Keywords

  • Circulating tumor cell
  • Coagulation
  • Tissue factor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Development of coagulation factor probes for the identification of procoagulant circulating tumor cells. / Tormoen, Garth W.; Cianchetti, Flor A.; Bock, Paul E.; McCarty, Owen.

In: Frontiers in Oncology, Vol. 2 SEP, Article 110, 2012.

Research output: Contribution to journalArticle

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