The role of S100A4 for bone metastasis in prostate cancer cells

Abstract Background Prostate cancers frequently metastasize to bone, where the best microenvironment for distant colonization is provided. Since osteotropic metastasis of prostate cancer a critical determinant patients’ survival, searches preventive measures are ongoing in field. Therefore, it important dissect mechanisms each step bone metastasis, including epithelial-mesenchymal transition (EMT) and cross-talk between metastatic niches cells. Methods In this study, we established highly bone-metastatic subline human cells by selecting bone-homing population PC3 after cardiac injection eight-week-old male BALB/c-nude mice. Then assessed proliferation, EMT characteristics, migration properties (mtPC3) comparison with parental To investigate role S100A4, performed gene knock-down lentiviral transduction, or treated recombinant S100A4 protein S100A4-neutralizing antibody. The effect on osteoclastogenesis was evaluated treatment pre-osteoclasts conditioned medium (CM) from Results mtPC3 secreted markedly high level showed elevated cell proliferation mesenchymal properties. increased traits inhibited knock-down, but not affected exogenous S100A4. Furthermore, released stimulated osteoclast development via surface receptor RAGE. Down-regulation neutralization CM attenuated cancer-induced osteoclastogenesis. Conclusion Altogether, our results suggest that intracellular promotes characteristics tumor cells, activates osteoclastogenesis, contributing osteolytic metastasis. Thus, upregulation might be key element regulating