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. 2009 Jul 21;100(11):1999–2005. doi: 10.1111/j.1349-7006.2009.01294.x

Figure 1.

Figure 1

 he vicious cycle of bone metastasis. Tumor cells intruding into the bone marrow produce factors such as parathyroid hormone‐related peptide (PTHrP) and interleukin‐6 (IL‐6), which stimulate osteoclastogenesis either directly or by stimulating receptor activator of nuclear factor‐κB ligand (RANKL) expression in osteoblasts. These lead to an increase of bone resorption, which in turn allows the release from the bone matrix of growth factors such as transforming growth factor‐β (TGF‐β) and insulin‐like growth factor‐1 (IGF‐1) that enhance tumor cell growth and metabolism. CAII, carbonic anhydrase II; Cath K, cathepsin K; M‐CSF, macrophage‐colony stimulating factor; MMP‐9, matrix metalloproteinase‐9; PDGF, platelet‐derived growth factor.