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Semin Thromb Hemost 2008; 34(2): 161-169
DOI: 10.1055/s-2008-1079256
© Thieme Medical Publishers

Role of Alternatively Spliced Tissue Factor in Pancreatic Cancer Growth and Angiogenesis

Maxim Signaevsky1 , Jennifer Hobbs2 , Jennifer Doll3 , Na Liu1 , Gerald A. Soff1
  • 1Division of Hematology/Oncology, SUNY Downstate Medical Center, Brooklyn, New York
  • 2St. Jude Children's Research Hospital, Memphis, Tennessee
  • 3Feinberg School of Medicine at Northwestern University, Chicago, Illinois
Further Information

Publication History

Publication Date:
21 July 2008 (online)

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ABSTRACT

Increased tissue factor (TF) expression is observed in many types of cancer, associated with more aggressive disease, and in thrombosis. The mechanism by which TF promotes tumor growth remains unclear. Anticoagulation has been shown to result in a trend toward improved survival; no direct antitumor effect has been shown in cancer patients. Alternatively spliced tissue factor (asTF) was recently described, in which exon 5 is deleted. Because of a frame-shift in exon 6, the transmembrane and cytoplasmic domains are replaced with a unique COOH-terminal domain, making asTF soluble. Both alternatively spliced human tissue factor (asHTF) and full-length tissue factor (flTF) are expressed in human pancreatic cancer lines and in pancreatic cancer specimens. We studied the role of asHTF and flTF in a mouse model of pancreatic cancer. Although lacking procoagulant activity, asTF promotes primary growth of human pancreatic cancer cells in mice and augments tumor-associated angiogenesis. This body of work suggests a new paradigm for the role of TF in pancreatic cancer: that asHTF contributes to cancer growth, independent of procoagulant activity.

KEYWORDS

Alternatively spliced human tissue factor - tissue factor - cancer progression - metastasis - angiogenesis

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Gerald J SoffM.D. 

Division of Hematology/Oncology, SUNY Downstate Medical Center

450 Clarkson Ave., Box 20, Brooklyn, NY 11203

Email: gsoff@downstate.edu

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