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Tissue Factor (TF) Expression and Angiogenesis in Tumor Progression and Inhibition of Tumor Growth by Anti-TF Antibodies in Human Tissue Factor Knock-In Mice | Abstract
ISSN: 2157-2518

Journal of Carcinogenesis & Mutagenesis
Open Access

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Research Article

Tissue Factor (TF) Expression and Angiogenesis in Tumor Progression and Inhibition of Tumor Growth by Anti-TF Antibodies in Human Tissue Factor Knock-In Mice

Amy L. Volk1*, Laura Johns1, Heena Beck2, Francis L. McCabe3, Patricia Rafferty1, Devon D. Egenolf1, Hillary Millar3, Jin Lu2, Barry Morse2, Mark Anderson3 and Peter J. Bugelski1

1Biologics Toxicology, Janssen Research & Development, LLC, Radnor, PA, USA

2Molecular Discovery Technology, Janssen Research & Development, LLC, Radnor, PA, USA

3Oncology Research, Janssen Research & Development, LLC, Radnor, PA, USA

*Corresponding Author:
Amy L. Volk
Biologics Toxicology
Biotechnology Center of Excellence
Janssen Research & Development
LLC, 145 King of Prussia Road
Radnor, PA 19087, USA
Tel: 610-407-8935
Fax: 610-889- 4525
E-mail: [email protected]

Received date: January 12, 2012; Accepted date: February 15, 2012; Published date: February 17, 2012

Citation: Volk AL, Johns L, Beck H, McCabe FL, Rafferty P, et al. (2012) Tissue Factor (TF) Expression and Angiogenesis in Tumor Progression and Inhibition of Tumor Growth by Anti-TF Antibodies in Human Tissue Factor Knock-In Mice. J Carcinogene Mutagene S7:001. doi: 10.4172/2157-2518.S7-001

Copyright: © 2012 Volk AL, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Tissue factor (TF) serves as the primary initiator of the extrinsic pathway of blood coagulation and mediates signaling via the protease activated receptor-2 (PAR2). TF is over-expressed in several tumor types and may facilitate tumor progression and angiogenesis. To test the hypothesis that inhibition of TF may have an anti-tumor effect, we induced pulmonary adenomas (PA) in human TF knock in (huTF-KI) mice with urethane and studied the relationship between expression of TF and mutations in K-ras with tumor progression and the effect of a monoclonal anti-TF antibody on growth of a transplantable lymphoma. Methods: huTF-KI mice received 10 weekly intraperitoneal (i.p.) injections of urethane and samples of lung were collected at six week intervals between weeks 10 and 28. Expression of TF and von Willibrand factor (vWF) in PA were studied by immunohistochemistry (IHC) and mutations in K-ras were studied by laser capture microdissection and polymerase chain reaction (LCM-PCR). Results: IHC showed that expression of TF and vWF increased as pulmonary epithelial hyperplasias and PA progressed. Dual staining TF and vWF showed that areas of high expression of TF correlated with the tumor vasculature and LCM-PCR showed that mutation of K-ras correlated with expression of TF and the angiogenic switch in PA. Finally, an anti-huTF monoclonal antibody slowed the growth of transplantable urethane-induced lymphomas. Conclusion: Taken together, these data suggest that expression of TF plays an important role in tumor progression and the angiogenic switch. These data also suggest that anti-TF antibodies may be a viable tumor immunotherapy

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