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

by Selleckchem | Aug 04 2023

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.

Comments:

The study you mentioned investigates the role of spondin 2 in prostate cancer-driven osteogenesis, particularly focusing on its effects on osteoblasts and the underlying molecular mechanisms. Here is a summary of the key findings:

1. Expression of Spondin 2 in Prostate Cancer: The study analyzed the expression of spondin 2 in prostate cancer samples obtained from the Gene Expression Omnibus (GEO) database. This suggests that spondin 2 may play a role in prostate cancer.

2. Effects of Spondin 2 on Osteoblasts: The supernatant of prostate cancer cells, which contains spondin 2, was used to treat a cell line called MC3T3-E1, which represents osteoblast precursor cells. The results indicated that spondin 2 promoted the expression of Osterix and Runx2, which are important markers of osteoblast differentiation and bone formation.

3. Inhibition of Spondin 2: To further understand the role of spondin 2, a spondin 2 antibody was used to neutralize its effect in vitro. This neutralization led to a decrease in the production of osteogenic factors, suggesting that spondin 2 is involved in promoting osteogenesis.

4. Involvement of the PI3K/AKT/mTOR Pathway: The study investigated the PI3K/AKT/mTOR pathway, which is a signaling pathway involved in various cellular processes, including cell growth and survival. Analysis of patient data from The Cancer Genome Atlas (TCGA) and in vitro experiments revealed that spondin 2 activates this pathway in prostate cancer cells. Western blot analysis confirmed the activation of PI3K/AKT/mTOR pathway components in response to spondin 2 treatment.

5. Role of Integrin Receptor α5β1: The study also explored the involvement of the integrin receptor α5β1 in spondin 2-mediated osteogenesis. Using an inhibitor of the spondin 2 receptor called ATN-161, the researchers demonstrated that blocking this receptor in MC3T3-E1 cells led to inhibition of osteogenesis.

Overall, the findings suggest that spondin 2 promotes osteogenesis through the activation of the PI3K/AKT/mTOR pathway in the context of prostate tumor progression. The involvement of the integrin receptor α5β1 indicates that this receptor is at least partially responsible for spondin 2's effects on osteoblasts. Further research in this area may help in understanding the mechanisms underlying bone metastasis in prostate cancer and potentially lead to the development of new therapeutic strategies.