title: Targeting the vasculature of colorectal carcinoma with a fused protein of (RGD)₃-tTF.
abstract: OBJECTIVE
  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 α(v)β₃ and tTF induce blood coagulation in tumor vessels.
  
  
  METHODS
  The bioactivities of (RGD)₃-tTF including coagulation activity, FX activation, and binding with integrin α(v)β₃ 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 α(v)β₃ 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).
  
  
  CONCLUSIONS
  (RGD)₃-tTF may be a promising strategy for the treatment of colorectal cancer.
authors.affiliation: Department of Surgical Oncology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province 361003, China.
authors.forename: Zheng-jie
authors.initials: ZJ
authors.lastname: Huang
authors.forename: Yilin
authors.initials: Y
authors.lastname: Zhao
authors.forename: Wei-yuan
authors.initials: WY
authors.lastname: Luo
authors.forename: Jun
authors.initials: J
authors.lastname: You
authors.forename: Shui-wen
authors.initials: SW
authors.lastname: Li
authors.forename: Wen-cheng
authors.initials: WC
authors.lastname: Yi
authors.forename: Sheng-yu
authors.initials: SY
authors.lastname: Wang
authors.forename: Jiang-hua
authors.initials: JH
authors.lastname: Yan
authors.forename: Qi
authors.initials: Q
authors.lastname: Luo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D039302:Integrin alphaVbeta3; D011993:Recombinant Fusion Proteins; C526680:tTF-RGD peptide