PTEN and melanoma: Moreover, downregulation of endogenous Entpd5 by transfection of human Entpd5 antisense in highly metastatic human A375sm melanoma cells, characterized by a lower level of PTEN and higher Entpd5, also reduced pulmonary metastasis significantly when cells were introduced into NSG mice by orthotopic footpad injection (p = 0.0136, Figures 5B-e, S9A).