Differential contribution of tissue factor and Factor XII to thrombin generation triggered by breast and pancreatic cancer cells

Int J Oncol. 2017 Dec;51(6):1747-1756. doi: 10.3892/ijo.2017.4172. Epub 2017 Oct 20.

Abstract

Most cancer cells trigger thrombin generation (TG) to various extent. In the present study, we dissected the mechanisms responsible for the procoagulant activity of pancreatic adenocarcinoma cells (BXPC3), a highly thrombogenic cancer type, and breast cancer cells (MCF7), a less thombogenic tumor type. TG of normal plasma was assessed by the Thrombinoscope (CAT®) in the presence or absence of cancer cells. TG was also assessed in plasma depleted of clotting factors, in plasma spiked with tissue factor (TF) and/or procoagulant phospholipids, in plasma spiked with an anti-TF monoclonal antibody or with corn trypsin inhibitor (CTI). The presence of alternatively spliced TF (asTF), TF activity (TFa) and cancer procoagulant (CP) levels were determined. TFa and asTF were highly expressed by BXPC3 cells, compared to MCF7 cells, while CP levels were higher in MCF7 cells. BXPC3 cells had a stronger effect on TG than MCF7 cells. Accordingly, anti-TF had more inhibitory activity on TG triggered by BXPC3 cells while CTI had more pronounced inhibitory effect on TG triggered by MCF7 cells. TG enhancement by both BXPC3 and MCF7 cells was mediated by FVII and intrinsic tenase while FXII and FXI were also important for MCF7 cells. The induction of TG by BXPC3 cells was mainly driven by the TF pathway while TG generation triggered by MCF7 cells was also driven by FXII activation. Therefore, hypercoagulability results from a combination of the inherent procoagulant properties of cancer cell-associated TF as well as of procoagulant phospholipids in the plasma microenvironment.

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Colonic Neoplasms / metabolism
  • Cysteine Endopeptidases / metabolism
  • Factor XII / metabolism*
  • Female
  • HCT116 Cells
  • HT29 Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • MCF-7 Cells
  • Neoplasm Proteins / metabolism
  • Ovarian Neoplasms / metabolism
  • Pancreatic Neoplasms / metabolism*
  • Platelet-Rich Plasma
  • Thrombin / biosynthesis*
  • Thromboplastin / biosynthesis
  • Thromboplastin / immunology
  • Thromboplastin / metabolism*

Substances

  • Antibodies, Monoclonal
  • Neoplasm Proteins
  • Factor XII
  • Thromboplastin
  • Thrombin
  • Cysteine Endopeptidases
  • cancer procoagulant