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Blood, 15 April 2004, Vol. 103, No. 8, pp. 3029-3037. Prepublished online as a Blood First Edition Paper on January 8, 2004; DOI 10.1182/blood-2003-10-3417. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-10-3417v1 103/8/3029    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hjortoe, G. M. Articles by Rao, L. V. M. Search for Related Content PubMed PubMed Citation Articles by Hjortoe, G. M. Articles by Rao, L. V. M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Tissue factor-factor VIIa–specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration Gertrud M. Hjortoe, Lars C. Petersen, Tatjana Albrektsen, Brit B. Sorensen, Peder L. Norby, Samir K. Mandal, Usha R. Pendurthi, and L. Vijaya Mohan Rao From the Biomedical Research Division, University of Texas Health Center at Tyler, TX; and Health Care Discovery, Novo Nordisk A/S, Maaloev and Bagsvaerd, Denmark. Tissue factor (TF), the cellular receptor for factor VIIa (FVIIa), besides initiating blood coagulation, is believed to play an important role in tissue repair, inflammation, angiogenesis, and tumor metastasis. Like TF, the chemokine interleukin-8 (IL-8) is shown to play a critical role in these processes. To elucidate the potential mechanisms by which TF contributes to tumor invasion and metastasis, we investigated the effect of FVIIa on IL-8 expression and cell migration in a breast carcinoma cell line, MDA-MB-231, a cell line that constitutively expresses abundant TF. Expression of IL-8 mRNA in MDA-MB-231 cells was markedly up-regulated by plasma concentrations of FVII or an equivalent concentration of FVIIa (10 nM). Neither thrombin nor other proteases involved in hemostasis were effective in stimulating IL-8 in these cells. Increased transcriptional activation of the IL-8 gene is responsible for increased expression of IL-8 in FVIIa-treated cells. PAR-2–specific antibodies fully attenuated TF-FVIIa–induced IL-8 expression. Additional in vitro experiments showed that TF-FVIIa promoted tumor cell migration and invasion, active site–inactivated FVIIa, and specific antibodies against TF, PAR-2, and IL-8 inhibited TF-FVIIa–induced cell migration. In summary, the studies described herein provide insight into how TF may contribute to tumor invasion. (Blood. 2004;103:3029-3037) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. M. Kuderer, T. L. Ortel, and C. W. Francis Impact of Venous Thromboembolism and Anticoagulation on Cancer and Cancer Survival J. Clin. Oncol., October 10, 2009; 27(29): 4902 - 4911. [Abstract] [Full Text] [PDF] R. S. Kasthuri, M. B. Taubman, and N. Mackman Role of Tissue Factor in Cancer J. Clin. Oncol., October 10, 2009; 27(29): 4834 - 4838. [Abstract] [Full Text] [PDF] R. Kaufmann, C. Oettel, A. Horn, K.-J. Halbhuber, A. Eitner, R. Krieg, K. Katenkamp, P. Henklein, M. Westermann, F. D. Bohmer, et al. 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