The attenuation of experimental lung metastasis by a bile acid acylated-heparin derivative.
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.
Park
Kyeongsoon
K
Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea.
Ki Lee
Seok
S
Hyun Son
Dai
D
Ah Park
Soo
S
Kim
Kwangmeyung
K
Won Chang
Hyo
H
Jeong
Eun-Jeong
EJ
Park
Rang-Woon
RW
Kim
In-San
IS
Chan Kwon
Ick
I
Byun
Youngro
Y
Kim
Sang Yoon
SY
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
D000970:Antineoplastic Agents; D001647:Bile Acids and Salts; D019040:E-Selectin; D019007:P-Selectin; D006493:Heparin