EPAS1 and metastatic neoplasm: We speculate that aggressive PCa, capsule-invading metastatic disease involves a hypoxic tumor microenvironment resulting in HIF-2α-increased eNAMPT secretion by epithelial cells [17], periprostatic adipocytes [31], PCa cells [16] and tumor-supporting tissue M2 macrophages whose generation we have shown is eNAMPT-enabled [32].