Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of (RGD)3-tTF
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 αvβ3 and tTF induce blood coagulation in tumor vessels. Methods. The bi...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1155/2013/637086 |
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| author | Zheng-jie Huang Yilin Zhao Wei-yuan Luo Jun You Shui-wen Li Wen-cheng Yi Sheng-yu Wang Jiang-hua Yan Qi Luo |
| author_facet | Zheng-jie Huang Yilin Zhao Wei-yuan Luo Jun You Shui-wen Li Wen-cheng Yi Sheng-yu Wang Jiang-hua Yan Qi Luo |
| author_sort | Zheng-jie Huang |
| collection | DOAJ |
| description | 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 αvβ3 and tTF induce blood coagulation in tumor vessels. Methods. The bioactivities of (RGD)3-tTF including coagulation activity, FX activation, and binding with integrin αvβ3 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 FX activation of (RGD)3-tTF were similar to that of TF (P>0.05) but different with that of RGD (P<0.05). (RGD)3-tTF presented a higher binding with αvβ3 than that of RGD and TF at the concentration of 0.2 μmol/L (P<0.05). (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 (P<0.05). Conclusion. (RGD)3-tTF may be a promising strategy for the treatment of colorectal cancer. |
| format | Article |
| id | doaj-art-e7c4081e3eef4f43abc41eaf0a113a0b |
| institution | Kabale University |
| issn | 1537-744X |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-e7c4081e3eef4f43abc41eaf0a113a0b2025-02-03T01:31:28ZengWileyThe Scientific World Journal1537-744X2013-01-01201310.1155/2013/637086637086Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of (RGD)3-tTFZheng-jie Huang0Yilin Zhao1Wei-yuan Luo2Jun You3Shui-wen Li4Wen-cheng Yi5Sheng-yu Wang6Jiang-hua Yan7Qi Luo8Department of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province 361003, ChinaDepartment of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province 361004, ChinaDepartment of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province 361003, ChinaDepartment of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province 361003, ChinaDepartment of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province 361003, ChinaDepartment of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province 361003, ChinaCancer Research Center of Medical School, Xiamen University, Xiamen, Fujian Province 361102, ChinaCancer Research Center of Medical School, Xiamen University, Xiamen, Fujian Province 361102, ChinaDepartment of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province 361003, ChinaPurpose. 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 αvβ3 and tTF induce blood coagulation in tumor vessels. Methods. The bioactivities of (RGD)3-tTF including coagulation activity, FX activation, and binding with integrin αvβ3 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 FX activation of (RGD)3-tTF were similar to that of TF (P>0.05) but different with that of RGD (P<0.05). (RGD)3-tTF presented a higher binding with αvβ3 than that of RGD and TF at the concentration of 0.2 μmol/L (P<0.05). (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 (P<0.05). Conclusion. (RGD)3-tTF may be a promising strategy for the treatment of colorectal cancer.http://dx.doi.org/10.1155/2013/637086 |
| spellingShingle | Zheng-jie Huang Yilin Zhao Wei-yuan Luo Jun You Shui-wen Li Wen-cheng Yi Sheng-yu Wang Jiang-hua Yan Qi Luo Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of (RGD)3-tTF The Scientific World Journal |
| title | Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of (RGD)3-tTF |
| title_full | Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of (RGD)3-tTF |
| title_fullStr | Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of (RGD)3-tTF |
| title_full_unstemmed | Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of (RGD)3-tTF |
| title_short | Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of (RGD)3-tTF |
| title_sort | targeting the vasculature of colorectal carcinoma with a fused protein of rgd 3 ttf |
| url | http://dx.doi.org/10.1155/2013/637086 |
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