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Semin Thromb Hemost 2008; 34(2): 170-181
DOI: 10.1055/s-2008-1079257
© Thieme Medical Publishers

Diverse Roles of Tissue Factor–Expressing Cell Subsets in Tumor Progression

Chloe Milsom1 , Joanne Yu1 , Linda May1 , Nathalie Magnus2 , Janusz Rak1 , 2
  • 1Henderson Research Centre, McMaster University, Hamilton, Ontario, Canada
  • 2Montreal Children's Hospital, McGill University, Montreal, Canada
Further Information

Publication History

Publication Date:
21 July 2008 (online)

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ABSTRACT

Oncogenic upregulation of tissue factor (TF) and release of TF-containing microvesicles play an important role in cancer-related coagulopathy (Trousseau's syndrome), angiogenesis, and disease progression. In addition, certain types of host cells (stromal cells, inflammatory cells, activated endothelium) may also express TF. Although the relative contribution of host-related versus tumor-related TF to tumor progression is not known, our recent studies indicate that the role of both sources of TF in tumor formation is complex and context-dependent. Disruption of TF expression/activity in cancer cells leads to tumor growth inhibition in immunodeficient mice, even in cases where TF overexpression is driven by potent oncogenes (K-ras or EGFR). Interestingly, TF expression in vivo appears to be influenced by many factors, including the level of oncogenic transformation, tumor microenvironment, and differentiation from cancer stem-like cells. We postulate that activation of TF signaling and coagulation may deliver growth-promoting stimuli (e.g., fibrin, thrombin, platelets) to dormant cancer stem cells (CSCs). Functionally, these influences may be tantamount to formation of a provisional (TF-dependent) cancer stem cell niche. As such, these changes may contribute to the involvement of CSCs in tumor growth, angiogenesis, and metastasis.

KEYWORDS

Tissue factor - oncogenes - cancer - angiogenesis - cancer stem cells - coagulation

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Janusz RakM.D. Ph.D. 

Montreal Children's Hospital Research Institute, 4060 Ste Catherine West, Montreal, QC

H3Z 3Z2, Canada

Email: janusz.rak@mcgill.ca