Inhibition of angiogenesis by a synthetic fusion protein VTF derived from vasostatin and tumstatin

Anticancer Drugs. 2014 Oct;25(9):1044-51. doi: 10.1097/CAD.0000000000000134.

Abstract

The inhibition of angiogenesis represents a potential strategy for antitumor therapy. A novel synthetic fusion protein VTF, composed of bioactive fragments from two different angiogenesis inhibitors, vasostatin and tumstatin with a (Gly-Ser-Gly)2 bridge, was generated using the pET-15b expression vector. The fusion protein VTF showed significantly enhanced efficacy in inhibiting human endothelial cell proliferation and tube formation and neovascularization on chick embryo chorioallantoic membrane. Moreover, VTF suppressed the growth of B16 melanoma and the formation of tumor blood vessels potently in vivo. These results indicated that the fusion protein containing the bioactive fragments of multiple angiogenesis inhibitors might be a promising therapeutic agent for tumor treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / genetics
  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Autoantigens / chemistry
  • Autoantigens / genetics*
  • Calreticulin / chemistry
  • Calreticulin / genetics*
  • Cell Line
  • Cell Proliferation / drug effects
  • Chick Embryo
  • Chorioallantoic Membrane / blood supply
  • Chorioallantoic Membrane / drug effects
  • Collagen Type IV / chemistry
  • Collagen Type IV / genetics*
  • Epithelial Cells
  • Escherichia coli
  • Genetic Vectors
  • Heterografts
  • Humans
  • Male
  • Melanoma, Experimental / blood supply
  • Melanoma, Experimental / drug therapy
  • Mice, Inbred BALB C
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Physiologic / drug effects
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / pharmacology
  • Recombinant Fusion Proteins / therapeutic use*
  • Skin / blood supply

Substances

  • Angiogenesis Inhibitors
  • Autoantigens
  • Calreticulin
  • Collagen Type IV
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • VTF fusion protein
  • type IV collagen alpha3 chain
  • vasostatin