Tissue factor and cancer

Pathophysiol Haemost Thromb. 2008;36(3-4):160-76. doi: 10.1159/000175154. Epub 2009 Jan 27.

Abstract

Tissue factor (TF), the key regulator of haemostasis and angiogenesis, is also involved in the pathology of several diseases, including cardiovascular, inflammatory and neoplastic conditions. In the latter, TF is upregulated by cancer cells, as well as by certain host cells, and it is the interactions between these distinct pools of TF-expressing cells that likely influence tumour progression in several ways. Furthermore, the release of TF microparticles into the circulation is thought to contribute to the systemic coagulopathies commonly observed in cancer patients. The direct regulation of TF by oncogenic events has provided a plausible explanation for the relatively common overexpression of TF in various cancers and its involvement in tumour growth, angiogenesis, metastasis and coagulopathy. However, this constitutive influence is modified by the tumour microenvironment, cellular interactions and host factors rendering TF expression patterns complex and heterogeneous. It appears that in many biological contexts TF plays a central role in disease progression and thereby potentially constitutes an attractive therapeutic target, especially in scenarios where the risk of bleeding can be avoided by selecting appropriate medications, refined dosing or by targeting the signalling component of TF activity. The efficacy and safety of such approaches still awaits clinical verification.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Blood Coagulation Factors / physiology
  • Blood Platelets / ultrastructure
  • Cell Transformation, Neoplastic / genetics
  • Cell-Derived Microparticles / physiology
  • Drug Delivery Systems
  • Genes, Tumor Suppressor
  • Hemostasis / physiology
  • Humans
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Neoplasm Metastasis
  • Neoplasm Proteins / physiology*
  • Neoplasms / blood
  • Neoplasms / complications
  • Neoplasms / genetics
  • Neoplasms / physiopathology*
  • Neovascularization, Pathologic / physiopathology
  • Oncogenes
  • Organ Specificity
  • Platelet Activation
  • Thrombophilia / blood
  • Thrombophilia / etiology*
  • Thrombophilia / physiopathology
  • Thromboplastin / physiology*

Substances

  • Antineoplastic Agents
  • Blood Coagulation Factors
  • Neoplasm Proteins
  • Thromboplastin