Prostate cancer is the leading cause of cancer death among men worldwide. Bone metastasis is one of the main problems arising from prostate cancer. Spondin 2 is a diagnostic marker specific for prostate cancer; however, the role of spondin 2 in prostate cancer‑driven osteogenesis remains unclear. The present study was carried out to explore the role of spondin 2 on prostate cancer cell‑induced osteogenesis. In the present study, the expression of spondin 2 was analyzed in prostate cancer samples obtained from Gene Expression Omnibus. The supernatant of prostate cancer cells was used to treat the osteoblast precursor MC3T3‑E1 cell line to determine the effect of spondin 2 on osteoblasts. The effect of spondin 2 on osteogenic factor production was also examined after neutralization with a spondin 2 antibody in vitro via reverse transcription‑quantitative PCR. Furthermore, the effect of spondin 2 on the PI3K/AKT/mTOR pathway was assessed using a patient dataset from The Cancer Genome Atlas and in vitro via western blot analysis. In addition, an inhibitor of spondin 2 receptor (ATN‑161) was used to explore the inhibition effect of spondin 2 receptor in MC3T3‑E1 cells. The results showed that spondin 2 promoted Osterix and Runx2 expression in osteoblasts, and this process was tightly associated with the activation of the PI3K/AKT/mTOR pathway. Moreover, it was demonstrated that the function of spondin 2 on prostate cancer‑driven osteogenesis at least partly relied on the integrin receptor α5β1. These results demonstrated that spondin 2 boosts osteogenesis via the PI3K/AKT/mTOR pathway under conditions of prostate tumor progression.
Keywords: PI3K; mTOR; osteoblast; prostate cancer; spondin 2.