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Semin Thromb Hemost 2004; 30(1): 21-30
DOI: 10.1055/s-2004-822968
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Oncogenes as Regulators of Tissue Factor Expression in Cancer: Implications for Tumor Angiogenesis and Anti-Cancer Therapy

Joanne L. Yu1 , Linda May1 , Petr Klement1 , Jeffrey I. Weitz1 , Janusz Rak1 , 2
  • 1Henderson Research Centre, Experimental Thrombosis Research, McMaster University, Hamilton, Ontario, Canada
  • 2Assistant Professor of Henderson Research Centre, Experimental Thrombosis Research, McMaster University, Hamilton, Ontario, Canada
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Publikationsverlauf

Publikationsdatum:
22. März 2004 (online)

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Up-regulation of tissue factor (TF) is often observed in cancer. TF is a cell-associated receptor for coagulation factor VII/VIIa, an interaction known to activate the coagulation cascade. At the same time, TF is also known as a mediator of intracellular signaling events that can alter gene expression patterns and cell behavior. Both aspects of TF activity are of possible relevance to tumor growth, metastasis, and angiogenesis, including up-regulation of vascular endothelial growth factor (VEGF). TF up-regulation is often observed on the surfaces of tumor-associated endothelial cells, inflammatory cells, and particularly on cancer cells themselves. In the last case, high TF levels may be associated with poor prognosis and parallel clinical (and genetic) tumor progression. We have proposed elsewhere that TF may be a target of oncogenic events in cancer. Here we discuss our observations suggesting that oncogene-targeting agents may down-regulate TF expression. Such is the effect of treatment with the neutralizing monoclonal antibody (C225) raised against the epidermal growth factor receptor (EGFR) in EGFR-dependent squamous cell carcinoma cells (A431). This two- to threefold TF down-regulation by C225 treatment is paralleled by a decrease in expression of VEGF. It is conceivable that TF participates in signals that regulate VEGF and angiogenesis triggered by activated oncogenic pathways. Therefore, direct targeting of TF in cancer should be considered in combination with other treatment modalities such as oncogene-directed therapies, antiangiogenic agents (e.g., VEGF antagonists), and anti-cancer chemotherapy.

KEYWORDS

Tissue factor - cancer - angiogenesis - oncogenes - EGFR

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Janusz RakM.D. Ph.D. 

Henderson Research Centre

Room 216, 711 Concession Street

Hamilton, Ontario, L8V 1C3, Canada

eMail: jrak@thrombosis.hhscr.org