Osteosarcoma is the second most common form of primary bone cancer and can be characterised by intense bone pain and a risk of the tumour spreading elsewhere in the body.

Background of the study:

Woven bone (also known as fibrous bone) is characterized by disorganised structures that make bone mechanically weak and is a common feature of osteosarcoma.

In recent decades, there has been a significant increase in clinical efforts to develop bone building agents that enhance bone regeneration by stimulating the activity of bone forming cells, the osteoblasts.

Semaphorin 3A (Sema3A) is a protein produced by bone cells that stimulates the formation of new bone, it encourages fracture healing and participates in the protection against bone loss in osteoporosis.

Dr Idris, with PhD student Daniëlle de Ridder, investigated whether Semaphorin 3A (Sema3A) also plays a role in osteosarcoma associated bone damage and metastasis, and whether its use could be explored as a new bone preserving therapeutic option.

Results of this Study:

Sema3A is produced by bone cells, it can be isolated and is also commercially available; therefore, experiments can be devised in which the protein is added to cells in the laboratory.

In a research model of osteosarcoma, the Sheffield team found that administration of Sema3A increased bone volume in both healthy and osteosarcoma affected tissues in mice. These effects were indicative of the bone protective effects of Sema3A.

When osteosarcoma cells engineered in the laboratory to over-produce Sema3A were used in this model, significantly less “woven”, disorganized cancerous bone was observed. Further investigations revealed that exposure to Sema3A produced by tumour cells, triggered the production of another protein called DKK1, which is a known potent inhibitor of bone formation.

The results indicate that application of Sema3A — or synthetic agents that mimic its action — in osteosarcoma may provide a win-win therapeutic approach that enhances healthy bone regeneration and reduces the formation of cancerous bone.

Further research is needed to assess the potential benefit of combining Sema3A with agents such as Denosumab (used to increase bone strength) or with conventional chemotherapeutic anti-cancer drugs such as Doxorubicin. This may especially be useful in patients where the tumour cannot be removed by surgery.

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