Tissue factor and cell signalling in cancer progression and thrombosis

W. Ruf, J. Disse, Tatiana Lobo, N. Yokota, F. Schaffner

Research output: Contribution to journalReview article

98 Citations (Scopus)

Abstract

The close link between coagulation activation and clinical cancer is well established and recent progress has defined underlying molecular pathways by which tumour cells interact with the haemostatic system to promote cancer progression. Tumour type-specific oncogenic transformations cause constitutive and hypoxia-dependent upregulation of tissue factor (TF) in cancer cells, but TF expressed by vascular, stromal and inflammatory cells also contributes to the procoagulant character of the tumour microenvironment. A growing body of genetic and pharmacological evidence implicates signalling by protease activated receptors (PARs) and specifically by tumour cell-expressed TF-VIIa-PAR2 in the induction of an array of proangiogenic and immune modulating cytokines, chemokines and growth factors. Specific inhibition of this pathway results in attenuated tumour growth and angiogenesis. PARs are increasingly recognised as targets for proteases outside the coagulation system and emerging evidence indicates that alternative protease signalling pathways synergise with the coagulation system to promote tumour growth, angiogenesis and metastasis. The elucidation of new therapeutic targets in tumour-promoting protease signalling pathways requires new diagnostic approaches to identify patients that will benefit from tailored therapy targeting procoagulant or signalling aspects of the TF pathway.

Original languageEnglish
Pages (from-to)306-315
Number of pages10
JournalJournal of Thrombosis and Haemostasis
Volume9
Issue number1 S
DOIs
Publication statusPublished - 1 Jul 2011
Externally publishedYes

Fingerprint

Thromboplastin
Thrombosis
Neoplasms
Proteinase-Activated Receptors
Peptide Hydrolases
Factor VIIa
Tumor Microenvironment
Hemostatics
Stromal Cells
Growth
Chemokines
Blood Vessels
Intercellular Signaling Peptides and Proteins
Up-Regulation
Pharmacology
Cytokines
Neoplasm Metastasis
Therapeutics

Keywords

  • Angiogenesis
  • Factor VII
  • Metastasis
  • Protease activated receptor
  • Tissue factor

ASJC Scopus subject areas

  • Hematology

Cite this

Tissue factor and cell signalling in cancer progression and thrombosis. / Ruf, W.; Disse, J.; Lobo, Tatiana; Yokota, N.; Schaffner, F.

In: Journal of Thrombosis and Haemostasis, Vol. 9, No. 1 S, 01.07.2011, p. 306-315.

Research output: Contribution to journalReview article

Ruf, W. ; Disse, J. ; Lobo, Tatiana ; Yokota, N. ; Schaffner, F. / Tissue factor and cell signalling in cancer progression and thrombosis. In: Journal of Thrombosis and Haemostasis. 2011 ; Vol. 9, No. 1 S. pp. 306-315.
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