Fig. 2.

Roles of Gal-3 in the bone microenvironment. In breast cancer bone metastasis, intact Gal-3 is the predominant form. Cancer-secreted Gal-3 exhibits dual properties in bone metastasis: (1) secreted Gal-3 mediates osteoclast fusion and (2) suppresses osteoblast differentiation, leading effectively to osteolytic bone remodeling. Consequently, in breast cancer bone metastasis, Gal-3 drives osteolytic bone remodeling along with other osteoclast stimulators such as PTHrP and IL-8, inducing intracellular signaling for osteoclast differentiation/maturation, e.g. cFOS, NF-κB, and NFATc1. On the other hand, in prostate cancer bone metastasis, cleaved Gal-3 is the major form, which reduces the potent function of intact Gal-3 and gives priority to other secretory factors controlling the bone tumor microenvironment such as osteoblast stimulators, BMP, Wnt, and FGF. In prostate cancer bone metastasis, osteoblast stimulation is generally predominant in the context of complex tumor/environment-derived factors, leading to osteoblastic signal activation such as SMAD (in BMP signaling), β-catenin, δPKC (in Wnt signaling), and MAPK (in FGF signaling), which induce osteoblast differentiation and bone matrix production. Consequently, these events result in osteosclerotic bone remodeling. The figure was produced using Servier Medical Art on www.servier.com with permission