In the present study, we demonstrated, for the first time, that PlGF is directly involved in the invasive and infiltrative behavior of malignant melanoma and that blockade of the activation of its cognate receptor, VEGFR-1, by D16F7 mAb counteracts melanoma properties that contribute to tumor spread by inhibiting cell adhesion to ECM components and transmigration through an endothelial monolayer. Here, FLT1 is linked to melanoma.