Recently,
salmosin, a novel
snake venom-derived
disintegrin containing the
Arg-Gly-Asp (RGD) sequence, was reported to be both antiangiogenic and antitumorigenic. The antitumor activity was substantiated by in vivo administration of recombinant
salmosin into mice bearing
tumors. However, it was difficult to prepare functionally active recombinant
salmosin and to maintain a therapeutically effective concentration of the
protein in the circulatory system by daily
injections. Hence, we have suggested that
salmosin gene transfer mediated by cationic
liposomes may be a practical alternative for
cancer treatment. Plasmids encoding the
salmosin gene were constructed and then transferred by means of cationic
liposomes into transformed human embryonic kidney (HEK) 293 cells. The transfected genes were able to produce functionally active
salmosin proteins in vitro. In fact, the expressed
salmosin remarkably inhibited proliferation of bovine capillary endothelial (BCE) cells and effectively inhibited the migration of highly metastatic B16BL6 mouse
melanoma cells. Neovascularization in chick chorio-allantoic membranes (CAM) and in
Matrigel implanted subcutaneously into mice was greatly inhibited in the presence of the expressed
salmosin. Based on these experimental results, we suggest that the antitumor effect induced by
salmosin gene transfection may be due to the antiangiogenic activity of the expressed
salmosin proteins.