Liposomes modified with a synthetic Arg-Gly-Asp mimetic inhibit lung metastasis of B16BL6 melanoma cells.
Administration of large amounts of synthetic peptides based on the Arg-Gly-Asp (RGD) sequence has been shown to suppress tumor metastasis. To overcome the rapid degradation of peptides in the circulation, an RGD mimetic, L-arginyl-6-aminohexanoic acid (NOK), was synthesized and conjugated with phosphatidylethanolamine (PE) (NOK-PE) for liposomalization. Cell adhesion assays revealed that B16BL6 murine melanoma cells adhered to immobilized NOK-PE. This adhesion was inhibited by addition of either soluble RGDS or NOK at similar concentration in a dose-dependent manner. Administration of NOK-PE liposomes (equivalent to ca. 500 microg RGD peptides) via the tail vein completely inhibited lung colonization of B 16BL6 cells. The same dose of soluble NOK was not effective in inhibition of the tumor metastasis. In addition, injection of NOK-PE liposomes via the tail vein inhibited spontaneous lung metastasis of B16BL6 cells from the primary tumor site in the hind footpad. These results suggest that NOK, a structural mimetic of RGD, is capable of suppressing metastasis by blockade of the binding of the integrins present on tumor cells to the RGD-containing extracellular matrix.
Kurohane
K
K
Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Yada, Japan.
Namba
Y
Y
Oku
N
N
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000138:chemical synthesis; D002448:Cell Adhesion / Q000187:drug effects; D004337:Drug Carriers; D005353:Fibronectins / Q000378:metabolism; D008081:Liposomes; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009842:Oligopeptides / Q000008:administration & dosage* / Q000138:chemical synthesis; D010714:Phosphatidylethanolamines; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004337:Drug Carriers; D005353:Fibronectins; D008081:Liposomes; D009842:Oligopeptides; D010714:Phosphatidylethanolamines; C047981:arginyl-glycyl-aspartic acid