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

  • Authors:
    • Aurélie Rousseau
    • Annette K. Larsen
    • Patrick Van Dreden
    • Michele Sabbah
    • Ismail Elalamy
    • Grigoris T. Gerotziafas
  • View Affiliations

  • Published online on: October 20, 2017     https://doi.org/10.3892/ijo.2017.4172
  • Pages:1747-1756
Metrics: PDF 0 views | HTML 0 views
0

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.

Related Articles

Journal Cover

December 2017
Volume 51 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Rousseau, A., Larsen, A.K., Van Dreden, P., Sabbah, M., Elalamy, I., & Gerotziafas, G.T. (2017). Differential contribution of tissue factor and Factor XII to thrombin generation triggered by breast and pancreatic cancer cells. International Journal of Oncology, 51, 1747-1756. https://doi.org/10.3892/ijo.2017.4172
MLA
Rousseau, A., Larsen, A. K., Van Dreden, P., Sabbah, M., Elalamy, I., Gerotziafas, G. T."Differential contribution of tissue factor and Factor XII to thrombin generation triggered by breast and pancreatic cancer cells". International Journal of Oncology 51.6 (2017): 1747-1756.
Chicago
Rousseau, A., Larsen, A. K., Van Dreden, P., Sabbah, M., Elalamy, I., Gerotziafas, G. T."Differential contribution of tissue factor and Factor XII to thrombin generation triggered by breast and pancreatic cancer cells". International Journal of Oncology 51, no. 6 (2017): 1747-1756. https://doi.org/10.3892/ijo.2017.4172