Whilst we can not exclude the contribution of various local and systemic factors implicated in the regulation of osteosarcoma cell – osteoblast crosstalk, the relative increase in secreted DKK1 by KHOS cells overexpressing Sema3A may provide a plausible mechanism for the differential effects of exogenous and tumour-derived Sema3A on ectopic bone formation in the model described. This evidence concerns the gene SEMA3A and osteosarcoma.