title: 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.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Electronic address: jon.vidar.gaustad@rr-research.no.
authors.forename: Jon-Vidar
authors.initials: JV
authors.lastname: Gaustad
authors.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Trude G
authors.initials: TG
authors.lastname: Simonsen
authors.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Lise Mari K
authors.initials: LM
authors.lastname: Andersen
authors.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Einar K
authors.initials: EK
authors.lastname: Rofstad
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003911:Dextrans / Q000737:chemistry; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005260:Female; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006801:Humans; D000069416:Intravital Microscopy; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology*; D010446:Peptide Fragments / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011414:Properdin / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D012235:Rhodamines / Q000737:chemistry; D012878:Skin Neoplasms / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D003911:Dextrans; D010446:Peptide Fragments; D010455:Peptides; D012235:Rhodamines; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; C000603977:properdistatin; D011414:Properdin; D049452:Green Fluorescent Proteins; C009434:tetramethylrhodamine isothiocyanate