The fibrinolytic system, through the activation of plasmin and matrix metalloproteinases (MMPs) [49], and the growth factors, neurotrophins, mediating in part via the activation of the degradative enzymes heparanase [47], are two of the mechanistic pathways shown to be responsible for the breakdown of the major protein and glycosaminoglycans components of the ECM respectively involved in the development of melanoma brain metastasis. This evidence concerns the gene PLG and melanoma.