|
|
Blood, 1 November 2004, Vol. 104, No. 9, pp. 2746-2751.
Prepublished online as a Blood First Edition Paper on July 20, 2004; DOI 10.1182/blood-2004-03-1047.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Role of endogenous thrombin in tumor implantation, seeding, and spontaneous metastasis
Liang Hu,
Merlin Lee,
Wendy Campbell,
Roman Perez-Soler, and
Simon Karpatkin
From the Department of Medicine and Kaplan Cancer Center, New York University School of Medicine, NY.
Tumor/host-generated thrombin (endogenous thrombin) was investigated with tumor growth and metastasis experiments in mice by the use of hirudin, a highly potent specific inhibitor of thrombin. Pretreatment with hirudin inhibited tumor implantation in nude or syngeneic mice, following subcutaneous injection of 2 human and 2 murine tumors. Hirudin induced a considerable lag period in the appearance of tumor growth, compared with phosphate-buffered saline (PBS) treatment, but had no effect on established tumor nodule growth in vivo or on tumor growth in vitro. Hirudin treatment induced central necrosis of the tumor nodule compared with no effect with PBS treatment. Greater protection was noted with longer duration of treatment. Tumor seeding into blood was examined with green fluorescent protein (GFP)-labeled tumor cells. Hirudin inhibited seeding into the blood as well as systemic organs which varied from complete protection to 15- to 32-fold in the blood and 17- to 395-fold in the lung. Hirudin inhibited spontaneous metastases from subcutaneously implanted tumor by reducing the number of tumor nodules in the lungs. Mouse survival in animals injected subcutaneously with highly aggressive 4T1 cells revealed 5 of 5 deaths of PBS-treated animals on day 40 compared with no deaths with hirudin treatment, with prolongation of survival with hirudin treatment of 16 days to more than 31 days. Thus, endogenous thrombin contributes to tumor implantation, seeding, and spontaneous metastasis. A potent antithrombin agent should be of clinical benefit to patients with cancer. (Blood. 2004;104:2746-2751)
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
C. Boccaccio and P. M. Comoglio
Genetic Link Between Cancer and Thrombosis
J. Clin. Oncol.,
October 10, 2009;
27(29):
4827 - 4833.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. L. Van Sluis, T. M.H. Niers, C. T. Esmon, W. Tigchelaar, D. J. Richel, H. R. Buller, C. J.F. Van Noorden, and C. A. Spek
Endogenous activated protein C limits cancer cell extravasation through sphingosine-1-phosphate receptor 1-mediated vascular endothelial barrier enhancement
Blood,
August 27, 2009;
114(9):
1968 - 1973.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Hu, J. M. Roth, P. Brooks, J. Luty, and S. Karpatkin
Thrombin Up-regulates Cathepsin D which Enhances Angiogenesis, Growth, and Metastasis
Cancer Res.,
June 15, 2008;
68(12):
4666 - 4673.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Hu, J. M. Roth, P. Brooks, S. Ibrahim, and S. Karpatkin
Twist Is Required for Thrombin-Induced Tumor Angiogenesis and Growth
Cancer Res.,
June 1, 2008;
68(11):
4296 - 4302.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Radjabi, K. Sawada, S. Jagadeeswaran, A. Eichbichler, H. A. Kenny, A. Montag, K. Bruno, and E. Lengyel
Thrombin Induces Tumor Invasion through the Induction and Association of Matrix Metalloproteinase-9 and {beta}1-Integrin on the Cell Surface
J. Biol. Chem.,
February 1, 2008;
283(5):
2822 - 2834.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Palumbo, K. E. Talmage, J. V. Massari, C. M. La Jeunesse, M. J. Flick, K. W. Kombrinck, Z. Hu, K. A. Barney, and J. L. Degen
Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and-independent mechanisms
Blood,
July 1, 2007;
110(1):
133 - 141.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Uusitalo-Jarvinen, T. Kurokawa, B. M. Mueller, P. Andrade-Gordon, M. Friedlander, and W. Ruf
Role of Protease Activated Receptor 1 and 2 Signaling in Hypoxia-Induced Angiogenesis
Arterioscler Thromb Vasc Biol,
June 1, 2007;
27(6):
1456 - 1462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Jain, M. Zuka, J. Liu, S. Russell, J. Dent, J. A. Guerrero, J. Forsyth, B. Maruszak, T. K. Gartner, B. Felding-Habermann, et al.
Platelet glycoprotein Ib{alpha} supports experimental lung metastasis
PNAS,
May 22, 2007;
104(21):
9024 - 9028.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Caunt, L. Hu, T. Tang, P. C. Brooks, S. Ibrahim, and S. Karpatkin
Growth-regulated oncogene is pivotal in thrombin-induced angiogenesis.
Cancer Res.,
April 15, 2006;
66(8):
4125 - 4132.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Stevenson, S. H. Choi, and A. Varki
Differential Metastasis Inhibition by Clinically Relevant Levels of Heparins--Correlation with Selectin Inhibition, Not Antithrombotic Activity
Clin. Cancer Res.,
October 1, 2005;
11(19):
7003 - 7011.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
