Osteocytes exhibited elevated Lrp5 expression in response to tumor cells, implying that osteocytes protect bone through canonical Wnt signaling. Notably, silencing Lrp5 in tumors inhibited tumor progression, while silencing Lrp5 in osteocytes in conditional knockout mice promoted tumor progression. The antitumor effect was also observed with osteocyte-derived CM that was pretreated with a Wnt-activating compound. Osteocytes overexpressing Lrp5 or β-catenin displayed strikingly elevated tumor-suppressive activity, accompanied by downregulation of tumor-promoting chemokines and upregulation of apoptosis-inducing and tumor-suppressing proteins such as p53. The results revealed that administration of osteocytes or their conditioned medium (CM) inhibited tumor progression and osteolysis. The role of Lrp5-mediated Wnt signaling was examined by overexpressing and silencing Lrp5 in osteocytes and establishing a conditional knockout mouse model. In animal experiments, mammary tumor cells were inoculated into the mammary fat pad and tibia. Here, we focused on Wnt signaling and evaluated tumor-osteocyte interactions.

Osteocytes are the most abundant cells in bone, which is a frequent site of breast cancer metastasis.

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