Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.7)
Index Copernicus  – 161.11; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2017, vol. 26, nr 8, November, p. 1219–1224

doi: 10.17219/acem/67760

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

A preliminary estimation of tissue factor pathway inhibitor (TFPI) and protein C in patients with intracranial tumors

Danuta Rość1,A,C,D,E, Ewa Grabarczyk1,A,B, Maciej Bierwagen2,A,B, Marcin Wierciński2,A,B, Krzysztof Góralczyk1,C, Beata Haor1,C, Barbara Ruszkowska-Ciastek1,C,E,F

1 Department of Pathophysiology, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Poland

2 Neurosurgery and Traumatology Ward, University Hospital No. 2 in Bydgoszcz, Poland

Abstract

Background. In patients with intracranial tumors, hypercoagulability is observed due to brain tissue and tumor cells being the source of tissue factor.
Objectives. The aim of the study was to assess tissue factor (TF), tissue factor pathway inhibitor (TFPI) and protein C in the plasma and tumor tissue homogenate in patients with intracranial tumors.
Material and Methods. The study included 77 patients; 24 patients were diagnosed with glioma, 20 patients with meningioma and 33 patients with metastatic tumors; mean age – 54 years. The material for the study was the plasma and tumor tissue homogenate sampled during surgery. The control group consisted of 30 controls; mean age – 51 years. In the plasma of all the participants and in tumor tissue homogenate, the concentrations of TF-Ag, TFPI-Ag and protein C activity, and the concentration of total protein were measured. The results were converted per mg of protein.
Results. In patients with intracranial tumors, elevated concentrations of TF-Ag, TFPI-Ag and protein C activity were noted, also after the conversion per mg of protein. A 100-fold higher concentration of TF per 1 mg of protein was found in tumor tissue compared to the patients’ plasma. In tumor tissue homogenate, a lower TFPI concentration and a lower protein C activity were recorded.
Conclusion. The study confirmed the essential prothrombotic properties in patients with intracranial tumors, expressed with an elevated TF level, as well as a tremendous amount of TF in tumor tissue homogenate derived from tumors. The elevated concentration of TFPI and protein C activity converted per mg of total protein should be analyzed in terms of their pleiotropic function, along with the participation in hemostasis control. It seems that the reduced protein C activity and low TFPI level are associated with the enormous TF value in tumor tissue homogenates.

Key words

tissue factor, tissue factor pathway inhibitor, protein C, intracranial tumors

References (30)

  1. Chu AJ. Tissue factor, blood coagulation, and beyond: An overview. Int J Inflam. 2011;2011:367284.
  2. Tang H, Fang J, Shu K, et al. Tissue factor/ FVII regulates doxorubicin-induced apoptosis in glioblastoma via activating PI3K/Akt signaling. Chinese-German J Clin Oncol. 2007;6:487–491.
  3. Magnus N, Meehan B, Garnier D, et al. The contribution of tumor and host tissue factor expression to oncogene-driven gliomagenesis. Bioch Biophys Res Communic. 2014;454:262–268.
  4. Wood JP, Ellery PE, Maroney SA, Mast AE. Biology of tissue factor pathway inhibitor. Blood. 2014;123:2934–2943.
  5. Opstad TB, Pettersen AA, Weiss T, Arnesen H, Seljeflot I. Gender differences of polymorphisms in the TF and TFPI genes, as related to phenotypes in patients with coronary heart disease and type-2 diabetes. Thromb J. 2010;8:7.
  6. Owens AP III, Mackman N. Tissue factor and thrombosis: The clot starts here. Thromb Haemost. 2010;104:432–439.
  7. Bouwens EA, Stavenuiter F, Mosnier LO. Mechanisms of anticoagulant and cytoprotective actions of the protein C pathway. J Thromb Haemost. 2013;11:242–253.
  8. Griffin JH, Zlokovic BV, Mosnier LO. Protein C anticoagulant and cytoprotective pathways. Int J Hematol. 2012;95:333–345.
  9. Gabre J, Chabasse C, Cao C, et al. Activated protein C accelerates venous thrombus resolution through heme oxygenase-1 induction. J Thromb Haemost. 2014;12:93–102.
  10. Cole M, Bromberg M. Tissue factor as a novel target for treatment of breast cancer. Oncologist. 2013;18:14–18.
  11. Perry JR. Thromboembolic disease in patients with high-grade glioma. Neuro Oncol. 2012;14:73–80.
  12. Magnus N, Garnier D, Meehan B, et al. Tissue factor expression provokes escape from tumor dormancy and leads to genomic alterations. Proc Natl Acad Sci USA. 2014;111:3544–3549.
  13. Monteiro RQ, Lima LG, Gonçalves NP, et al. Hypoxia regulates the expression of tissue factor pathway signaling elements in a rat glioma model. Oncol Lett. 2016;12:315–322.
  14. Butenas S. Tissue factor structure and function. Stientifica. 2012;2012:964862.
  15. Han X, Guo B, Li Y, Zhu B. Tissue factor in tumor microenvironment: A systematic review. J Hematol Oncol. 2014;7:54.
  16. Ruf W, Disse J, Carneiro-Lobo TC, Yokota N, Schaffner F. Tissue factor and cell signalling in cancer progression and thrombosis. J Thromb Haemost. 2011;9:306–315.
  17. van den Berg YW, Osanto S, Reitsma PH, Versteeg HH. The relationship between tissue factor and cancer progression: Insights from bench and bedside. Blood. 2012;119:924–932.
  18. Cai Y, Wu J, Li Z, Long Q. Mathematical modelling of a brain tumour initiation and early development: A coupled model of glioblastoma growth, pre-existing vessel co-option, angiogenesis and blood perfusion. PLoS One. 2016;11:e0150296.
  19. Rak J. Micropaticles in cancer. Semin Thromb Haemost. 2010;36(8):888–906.
  20. Skog J, Wűrdinger T, van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10:1470–1476.
  21. Sartori MT, Della Puppa A, Ballin A, et al. Circulating microparticles of glial origin and tissue factor bearing in high-grade glioma: A potential prothrombotic role. Thromb Haemost. 2013;110:378–385.
  22. Iversen N, Lindahl AK, Abildgaard U. Elevated plasma levels of the factor Xa-TFPI complex in cancer patients. Thromb Res. 2002;105:33–36.
  23. Assy N, Schlesinger S, Hussein O. Elevated plasma protein C levels correlate with the presence of fatty liver (NASH and NAFLD). GUT. 2005;54:729.
  24. Agewall S, Bokemark L, Wikstrand J, Lindahl A, Fagerberg B. Insulin sensitivity and haemostatic factors in clinically healthy 58-year old men. Throm Haemost. 2000;84:571–575.
  25. D’Angelo A, Landi G, Vigano’D’Angelo S, et al. Protein C in acute stroke. Stroke. 1988;19:579–583.
  26. Beaulieu LM, Church FC. Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1. Exp Cell Res. 2007;313:677–687.
  27. Schaffner F, Yokota N, Carneiro-Lobo T, et al. Endothelial protein C receptor function in murine and human breast cancer development. Plos One. 2013;8(4):e61071.
  28. Minuk L, Lazo-Langner A, Kovacs J, Robbins M, Morrow B, Kovacs M. Normal levels of protein C and protein S tested in the acute phase of a venous thromboembolic event are not falsely elevated. Thromb J. 2010;8:1–4.
  29. Ahamed J, Belting M, Ruf W. Regulation of tissue factor-induced signaling by endogenous and recombinant tissue factor pathway inhibitor 1. Blood. 2005;105:2384–2391.
  30. Amirkhosravi A, Meyer T, Amaya M, et al. The role of tissue factor pathway inhibitor in tumor growth and metastasis. Sem Throm Haemost. 2007;33:643–652.