title: Tumor endothelial cell targeted cyclic RGD-modified heparin derivative: inhibition of angiogenesis and tumor growth.
abstract: OBJECTIVE
  We prepared tumor endothelium targeted cRGD-modified heparin derivative (cRGD-HL) by coupling heparin-lithocholic acid (HL) with cRGDyK, and evaluated inhibition effects of cRGD-HL on angiogenesis and tumor growth.
  
  
  METHODS
  To evaluate antiangiogenic activity of cRGD-HL, we performed tests on endothelial cell adhesion and migration to vitronectin, tube formation, binding affinity to purified alpha(v)beta(3) integrin, and in vivo Matrigel plug assay. The antitumor activity of cRGD-HL was also evaluated by monitoring tumor growth and microvessel formation in squamous cell carcinoma (SCC7) tumor.
  
  
  RESULTS
  The cRGD-HL significantly inhibited adhesion and migration of endothelial cells to vitronectin, and tubular structures of endothelial cells. Compared to cRGDyK and HL, cRGD-HL has high binding affinity to purified alpha(v)beta(3) integrin. The enhanced antiangiogenic effect of cRGD-HL was confirmed in Matrigel assay by showing the significant inhibition of bFGF-driven angiogenesis and blood vessel formation. It was thought that potent antiangiogenic effect of cRGD-HL was probably due to the interference of alpha(v)beta(3)-mediated interaction, resulting in the enhanced antitumoral activity against SCC7 tumor.
  
  
  CONCLUSIONS
  These results demonstrated that cRGD-modified heparin derivative enhanced anti-angiotherapeutic effects against solid tumor, and therefore, it could be applied to treat various cancers and angiogenic diseases as a potent angiogenesis inhibitor.
authors.affiliation: Biomedical Research Center, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul, South Korea. kspark@kist.re.kr
authors.forename: Kyeongsoon
authors.initials: K
authors.lastname: Park
authors.forename: Yoo-Shin
authors.initials: YS
authors.lastname: Kim
authors.forename: Gee Young
authors.initials: GY
authors.lastname: Lee
authors.forename: Rang-Woon
authors.initials: RW
authors.lastname: Park
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D006493:Heparin / Q000031:analogs & derivatives*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008095:Lithocholic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009842:Oligopeptides / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D008095:Lithocholic Acid; C047981:arginyl-glycyl-aspartic acid; D006493:Heparin