In a non-tumor model, ROSI has been reported to inhibit the activities of those two factors; in myeloma cell line, ROSI inhibits insulin-like growth factor 1 (IGF-1) or HIF-1α, which could boost VEGF’s pro-angiogenesis effects, via PI3K/AKT and ERK signaling in a PPAR-γ-dependent fashion (105, 106). Here, IGF1 is linked to plasma cell myeloma.