Prostate cancer cell‑derived spondin 2 boosts osteogenic factor levels in osteoblasts via the PI3K/AKT/mTOR pathway

Abstract

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.

The biological functions and related signaling pathways of SPON2

“…Wang H et al. discovered that SPON2 derived from prostate cancer (PRAD) cells significantly enhances the expression of osteogenic factors in osteoblasts through the PI3K/AKT/mTOR signaling pathway ( 69 ). Bell SM et al.…”

“…JinYR et al revealed that SPON2 exerts a regulatory role in the morphogenesis of midfacial, limb, and lung structures during embryonic development, with this regulation being mediated via the WNT/ b-catenin signaling pathway (17,18). Wang H et al discovered that SPON2 derived from prostate cancer (PRAD) cells significantly enhances the expression of osteogenic factors in osteoblasts through the PI3K/AKT/mTOR signaling pathway (69). Bell SM et al identified a severe hypomorphic SPON2 allele that was associated with pulmonary abnormalities.…”