This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yoshida, E. Articles by Kwaan, H. C. Search for Related Content PubMed PubMed Citation Articles by Yoshida, E. Articles by Kwaan, H. C.

Enhancement of the Expression of Urokinase-Type Plasminogen Activator from PC-3 Human Prostate Cancer Cells by Thrombin¹

Department of Medicine, Hematology/Oncology Division, Northwestern University Medical School, and VA Lakeside Medical Center, Chicago, Illinois 60611 [E. Y., E. N. V., D. O., H. C. K.], and Department of Physiology, Miyazaki Medical College, Miyazaki 889-16, Japan [H. M.]

The presence of procoagulants and fibrin deposition have been demonstrated in malignant tumors. Although thrombin, a key enzyme in coagulation, has other various biological functions, the significance of its presence in tumors is not known. We studied the effects of thrombin on the expression of urokinase-type plasminogen activator (uPA) which is known to play a role in tumor invasion, using a human prostate cancer cell line PC-3. Human -thrombin added to cultures of PC-3 produced a dose-dependent and time-dependent increased secretion of uPA that was greatest at 3–6 h after exposure to thrombin. Increase in uPA antigen paralleled the increase in mRNA level, which reached a maximum at 4 h. Thrombin showed the maximum effect on uPA expression at a concentration 1–2 units/ml. Zymography showed that transient exposure to thrombin induced an increase in fibrinolytic activity which could be quenched by anti-uPA antibody. The thrombin receptor-activating peptide also caused an increase in uPA protein and mRNA level, indicating the presence of the same thrombin specific receptor on PC-3 cells as on platelets and endothelial cells. Thrombin did not affect the expression of other components of the plasminogen activation system, tissue-type plasminogen activator and type-1 plasminogen activator inhibitor, and uPA receptor. These results indicate that thrombin increases uPA expression selectively by the stimulation of a functional thrombin receptor on PC-3 cells. Since uPA is known to play a role in pericellular proteolysis of extracellular matrix, thrombin may be involved in the regulation of tumor invasion and metastasis.

¹ This work is supported in part by a VA Merit Review Research Grant.

² Present address: Department of Physiology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-16, Japan.

³ To whom requests for reprints should be addressed, at Hematology/Oncology Division, VA Lakeside Medical Center, 333 East Huron, Chicago, IL 60611.

Received 2/28/94. Accepted 4/20/94.

This article has been cited by other articles:

				G. J. Mize, W. Wang, and T. K. Takayama Prostate-Specific Kallikreins-2 and -4 Enhance the Proliferation of DU-145 Prostate Cancer Cells through Protease-Activated Receptors-1 and -2 Mol. Cancer Res., June 1, 2008; 6(6): 1043 - 1051. [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]

				P. Kelly, L. N. Stemmle, J. F. Madden, T. A. Fields, Y. Daaka, and P. J. Casey A Role for the G12 Family of Heterotrimeric G Proteins in Prostate Cancer Invasion J. Biol. Chem., September 8, 2006; 281(36): 26483 - 26490. [Abstract] [Full Text] [PDF]

				S. Niimi, M. Harashima, K. Takayama, M. Hara, M. Hyuga, T. Seki, T. Ariga, T. Kawanishi, and T. Hayakawa Thrombomodulin Enhances the Invasive Activity of Mouse Mammary Tumor Cells J. Biochem., May 1, 2005; 137(5): 579 - 586. [Abstract] [Full Text] [PDF]

				C. Tellez, M. McCarty, M. Ruiz, and M. Bar-Eli Loss of Activator Protein-2{alpha} Results in Overexpression of Protease-activated Receptor-1 and Correlates with the Malignant Phenotype of Human Melanoma J. Biol. Chem., November 21, 2003; 278(47): 46632 - 46642. [Abstract] [Full Text] [PDF]

				M. A. Helenius, O. R. Saramaki, M. J. Linja, T. L. J. Tammela, and T. Visakorpi Amplification of Urokinase Gene in Prostate Cancer Cancer Res., July 1, 2001; 61(14): 5340 - 5344. [Abstract] [Full Text] [PDF]

				T. Takeuchi, M. A. Shuman, and C. S. Craik Reverse biochemistry: Use of macromolecular protease inhibitors to dissect complex biological processes and identify a membrane-type serine protease in epithelial cancer and normal tissue PNAS, September 28, 1999; 96(20): 11054 - 11061. [Abstract] [Full Text] [PDF]

				M. L. Nierodzik, K. Chen, K. Takeshita, J.-J. Li, Y.-Q. Huang, X.-S. Feng, M. R. D'Andrea, P. Andrade-Gordon, and S. Karpatkin Protease-Activated Receptor 1 (PAR-1) Is Required and Rate-Limiting for Thrombin-Enhanced Experimental Pulmonary Metastasis Blood, November 15, 1998; 92(10): 3694 - 3700. [Abstract] [Full Text] [PDF]

				T. Takeuchi, J. L. Harris, W. Huang, K. W. Yan, S. R. Coughlin, and C. S. Craik Cellular Localization of Membrane-type Serine Protease 1 and Identification of Protease-activated Receptor-2 and Single-chain Urokinase-type Plasminogen Activator as Substrates J. Biol. Chem., August 18, 2000; 275(34): 26333 - 26342. [Abstract] [Full Text] [PDF]