Pharmaceutical Research

, 25:2786

Tumor Endothelial Cell Targeted Cyclic RGD-modified Heparin Derivative: Inhibition of Angiogenesis and Tumor Growth

  • Kyeongsoon Park
  • Yoo-Shin Kim
  • Gee Young Lee
  • Rang-Woon Park
  • In-San Kim
  • Sang Yoon Kim
  • Youngro Byun
Research Paper

DOI: 10.1007/s11095-008-9643-y

Cite this article as:
Park, K., Kim, YS., Lee, G.Y. et al. Pharm Res (2008) 25: 2786. doi:10.1007/s11095-008-9643-y



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.


To evaluate antiangiogenic activity of cRGD-HL, we performed tests on endothelial cell adhesion and migration to vitronectin, tube formation, binding affinity to purified αvβ3 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.


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 αvβ3 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 αvβ3-mediated interaction, resulting in the enhanced antitumoral activity against SCC7 tumor.


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.


angiogenesis heparin derivative lithocholic acid RGD SCC7 



basic fibroblast growth factor


extracellular matrix


extracellular signal-regulated kinase


fibroblast growth factor receptor


heparin-lithocholic acid


human umbilical vein endothelial cells


mitogen-activated protein kinase


squamous cell carcinoma

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Kyeongsoon Park
    • 1
  • Yoo-Shin Kim
    • 2
  • Gee Young Lee
    • 3
  • Rang-Woon Park
    • 2
  • In-San Kim
    • 2
  • Sang Yoon Kim
    • 4
  • Youngro Byun
    • 3
  1. 1.Biomedical Research CenterKorea Institute of Science and TechnologySeoulSouth Korea
  2. 2.Department of Biochemistry and Cell Biology and Cell and Matrix Research Institute, School of MedicineKyungpook National UniversityDaeguSouth Korea
  3. 3.College of PharmacySeoul National UniversitySeoulSouth Korea
  4. 4.Department of Otolaryngology–Head and Neck Surgery, Asan Medical Center, College of MedicineUniversity of UlsanSeoulKorea

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