Thrombospondin-1 domain-containing peptide properdistatin improves vascular function in human melanoma xenografts

Microvasc Res. 2015 Mar:98:159-65. doi: 10.1016/j.mvr.2014.02.005. Epub 2014 Feb 17.

Abstract

Properdistatin is a novel peptide derived from the thrombospondin-1 domain of the plasma protein properdin. The purpose of this study was to investigate the effect of properdistatin treatment on the morphology and function of tumor vasculature. A-07 human melanoma xenografts grown in dorsal window chambers were used as preclinical model. Tumors were treated with 80 mg/kg/day properdistatin or vehicle for 4 days. Morphologic parameters of tumor vascular networks were assessed from high-resolution transillumination images, and tumor blood supply time and plasma velocities were assessed from first-pass imaging movies recorded after a bolus of 155 kDa tetramethylrhodamine isothiocyanate-labeled dextran had been administered intravenously. Properdistatin-treated tumors showed reduced density of small-diameter vessels, reduced blood supply time, and increased plasma velocities. In conclusion, properdistatin treatment inhibited angiogenesis and improved vascular function in A-07 tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Dextrans / chemistry
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / pathology*
  • Female
  • Green Fluorescent Proteins / chemistry
  • Humans
  • Intravital Microscopy
  • Melanoma / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / pathology*
  • Peptide Fragments / chemistry*
  • Peptides / chemistry*
  • Properdin / chemistry*
  • Protein Structure, Tertiary
  • Rhodamines / chemistry
  • Skin Neoplasms / metabolism*
  • Thrombospondin 1 / chemistry*
  • Vascular Endothelial Growth Factor A / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Dextrans
  • Peptide Fragments
  • Peptides
  • Rhodamines
  • Thrombospondin 1
  • Vascular Endothelial Growth Factor A
  • properdistatin
  • Properdin
  • Green Fluorescent Proteins
  • tetramethylrhodamine isothiocyanate