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

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.

• Authors: Jon-Vidar Gaustad, Trude G Simonsen, Lise Mari K Andersen, Einar K Rofstad
• Journal: Microvascular research (Microvasc Res) Vol. 98 Pg. 159-65 (Mar 2015) ISSN: 1095-9319 [Electronic] United States
• PMID: 24555949 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• Animals
• Cell Line, Tumor
• Dextrans (chemistry)
• Endothelium, Vascular (drug effects, 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