This type of dual action has also been reported with interleukin 8, levels of which correlate with increased bone metastasis.22 In the vicious cycle model of bone metastasis, PTHrP secretion from tumor cells is further stimulated by bone-latent factors, such as TGF-β, released upon matrix resorption by osteoclasts.2,23 Whether S100A4 stimulation of osteoclasts would lead to further induction of S100A4 in tumor cells, forming another type of vicious cycle in bone-metastatic environments, is a question to be resolved. The gene discussed is TGFB1; the disease is neoplasm.