title: The attenuation of experimental lung metastasis by a bile acid acylated-heparin derivative.
abstract: 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-alpha-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.
authors.affiliation: Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea.
authors.forename: Kyeongsoon
authors.initials: K
authors.lastname: Park
authors.forename: Seok
authors.initials: S
authors.lastname: Ki Lee
authors.forename: Dai
authors.initials: D
authors.lastname: Hyun Son
authors.forename: Soo
authors.initials: S
authors.lastname: Ah Park
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Hyo
authors.initials: H
authors.lastname: Won Chang
authors.forename: Eun-Jeong
authors.initials: EJ
authors.lastname: Jeong
authors.forename: Rang-Woon
authors.initials: RW
authors.lastname: Park
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.forename: Ick
authors.initials: I
authors.lastname: Chan Kwon
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D002448:Cell Adhesion; D002460:Cell Line; D019040:E-Selectin / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006493:Heparin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008422:Materials Testing; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental; D019007:P-Selectin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001647:Bile Acids and Salts; D019040:E-Selectin; D019007:P-Selectin; D006493:Heparin