The attenuation of experimental lung metastasis by a bile acid acylated-heparin derivative

Kyeongsoon Park, Seok Ki Lee, Dai Hyun Son, Soo Ah Park, Kwangmeyung Kim, Hyo Won Chang, Eun jeong Jeong, Rang Woon Park, In San Kim, Ick Chan Kwon, Youngro Byun, Sang Yoon Kim

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


The inhibitory efficacies of new bile acid acylated-heparin derivative (heparin-DOCA) were evaluated on experimental lung metastasis. We evaluated the effect of heparin-DOCA on intercellular interactions including those between B16F10 and thrombin-activated platelets and TNF-α-activated HUVECs, and between B16F10 and immobilized mouse P-selectin. In addition, the inhibitory effects of heparin-DOCA on adhesion and invasion of B16F10 to Matrigel were studied. In an animal mouse study, the blood clot formation and the retention of red fluorescence protein (RFP)-B16F10 in lungs were assessed after heparin-DOCA and RFP-B16F10 intravenous administration. Furthermore, we investigated the anti-metastatic effect of heparin-DOCA against lung metastasis induced by B16F10 and SCC7. Heparin-DOCA inhibited intercellular interactions between B16F10 and activated platelets or activated HUVECs by blocking P- and E-selectin-mediated interactions. Moreover, it reduced adhesion and invasion of B16F10 to ECM, thereby affecting the reduction of early retention of B16F10 in the lung. Heparin-DOCA attenuated lung colony formation on the surfaces and in interior of the lung, and attenuated metastasis by B16F10 and SCC7. These results suggest that heparin-DOCA may have potentials as therapeutic agent that prevents tumor metastasis and progression.

Original languageEnglish
Pages (from-to)2667-2676
Number of pages10
Issue number16
StatePublished - Jun 2007

Bibliographical note

Funding Information:
This work was supported by the Next Generation New Technology Development Program of the Korean Ministry of Commerce, Industry, and Energy (Grant no. # 10011353), Asan Institute for Life Science (2002-073) and the Ministry of Science and Technology F104AA010009-06A0101-00910 in Korea.


  • Adhesion
  • B16F10 melanoma
  • Bile acid acylated-heparin derivative
  • Invasion
  • Lung metastasis


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