Salmosin is a novel
disintegrin containing the
Arg-Gly-Asp sequence that significantly inhibits platelet aggregation,
basic fibroblast growth factor-induced endothelial cell proliferation, and
tumor progression by antagonizing
integrin-mediated cell interactions. Previously, it was shown that daily administration of
salmosin was able to inhibit
tumor-derived angiogenesis and adherence and proliferation of
tumor cells, resulting in suppression of
tumor progression. However, it is very difficult to maintain a therapeutic level of
salmosin in the blood by systemic administration of the
protein. Hence, an alternative strategy for antiangiogenic
cancer therapy, based on the in vivo expression of the
salmosin gene administered with cationic
liposomes, was investigated. The
salmosin peptides expressed in vitro inhibited the proliferation of bovine capillary endothelial cells in a dose-dependent manner, presumably as a result of inhibition of cell adhesion mediated via alpha(v)
beta(3) integrin. Subcutaneous administration of the
salmosin gene resulted in systemic expression of the gene product and concomitant inhibition of the growth of B16BL6
melanoma cells. Suppression of pulmonary
metastases, verified by experimental and spontaneous
metastasis models in mice, also resulted from
salmosin gene treatment. These results suggest that administration of the
salmosin gene complexed to cationic
liposomes is effective in maintaining antiangiogenic
salmosin at an effective therapeutic level and may be clinically applicable to anticancer gene therapy.