MMP12 and chondrosarcoma: In concert with our findings, IGF-2 is also reported to activate the pathways of PI3-K during chondrogenesis.40 Furthermore, IGF-2 is critical for activating MMP-12 in human chondrosarcomas.26 IGF-1, which belongs to the same protein family, has also been reported to be an upstream component of the PI3-K and AKT pathways in various experimental models.41 However, Arvisais et al.42 reported that PGF2α represses the IGF-1-stimulated activation of the PI3-K and AKT signaling pathways by stimulating the expression of ERK in the corpus luteum.