| Endogenous ADAM (A&barbelow D&barbelowisintegrin A&barbelownd M&barbelowetalloproteinase) proteins are known to contain a disintegrin-like domain which allows them to bind to integrins. The disintegrin domain of ADAM15 contains an RGD motif, a characteristic which makes it very similar to true snake venom disintegrins, that consistently have shown anti-angiogenic effects in various in vitro and in vivo models. In this study, we explored the anti-angiogenic effects of a human disintegrin, the disintegrin-like domain of ADAM15. This small polypeptide was made recombinantly in the Markland laboratory, encapsulated in liposomes and used for in vivo testing in a MDA-MB-231orthotopic breast carcinoma xenograft model. Our results show that the liposomal formulation of ADAM15 disintegrin (LMAP15) in vivo, increases host survival, decreases tumor size and decreases microvessel density relative to control animals. These findings underscore the potential of LMAP15 as a novel anti-angiogenic form of treatment in breast cancer. |
