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The Scientific World Journal
Volume 2013, Article ID 637086, 11 pages
http://dx.doi.org/10.1155/2013/637086
Research Article

Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of -tTF

1Department of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province 361003, China
2Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province 361004, China
3Cancer Research Center of Medical School, Xiamen University, Xiamen, Fujian Province 361102, China

Received 23 March 2013; Accepted 8 May 2013

Academic Editors: E. Z. Dajani and C. Rizzetto

Copyright © 2013 Zheng-jie Huang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose. Truncated tissue factor (tTF) fusion protein targeting tumor vasculature can induce tumor vascular thrombosis and necrosis. Here, we generated (RGD)3-tTF in which three arginine-glycine-aspartic (RGD) targeting integrin and tTF induce blood coagulation in tumor vessels. Methods. The bioactivities of (RGD)3-tTF including coagulation activity, activation, and binding with integrin were performed. The fluorescent labeled (RGD)3-tTF was intravenously injected into tumor-bearing mice and traced in vivo. The tumor growth, volume, blood vessel thrombosis, tumor necrosis, and survival time of mice treated with (RGD)3-tTF were evaluated. Results. The clotting time and activation of (RGD)3-tTF were similar to that of TF ( ) but different with that of RGD ( ). (RGD)3-tTF presented a higher binding with than that of RGD and TF at the concentration of 0.2  mol/L ( ). (RGD)3-tTF could specifically assemble in tumor and be effective in reducing tumor growth by selectively inducing tumor blood vessels thrombosis and tumor necrosis which were absent in mice treated with RGD or TF. The survival time of mice treated with (RGD)3-tTF was higher than that of mice treated with TF or RGD ( ). Conclusion. (RGD)3-tTF may be a promising strategy for the treatment of colorectal cancer.