Tissue Factor: A Conventional or Alternative Target in Cancer Therapy

Clin Chem. 2016 Apr;62(4):563-70. doi: 10.1373/clinchem.2015.241521. Epub 2016 Feb 19.

Abstract

Background: Tissue factor (TF) is an evolutionary conserved glycoprotein that plays an important role in the pathogenesis of cancer. TF is expressed in 2 naturally occurring protein isoforms, membrane-bound full-length (fl)TF and soluble alternatively spliced (as)TF. Both isoforms have been shown to affect a variety of pathophysiologically relevant functions, such as tumor-associated angiogenesis, thrombogenicity, tumor growth, and metastasis. Therefore, targeting TF either by direct inhibition or indirectly, i.e., on a posttranscriptional level, offers a novel therapeutic option for cancer treatment.

Content: In this review we summarize the latest findings regarding the role of TF and its isoforms in cancer biology. Moreover, we briefly depict and discuss the therapeutic potential of direct and/or indirect inhibition of TF activity and expression for the treatment of cancer.

Summary: asTF and flTF play important and often distinct roles in cancer biology, i.e., in thrombogenicity and angiogenesis, which is mediated by isoform-specific signal transduction pathways. Therefore, both TF isoforms and downstream signaling are promising novel therapeutic targets in malignant diseases.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Proliferation / drug effects
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / prevention & control
  • Protein Isoforms
  • Protein Processing, Post-Translational / drug effects
  • Thromboplastin / antagonists & inhibitors*
  • Thromboplastin / genetics

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Protein Isoforms
  • Thromboplastin