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Table 1 Pro-osteolytic tumor-secreted factors and their described role in the pathogenesis of osteolytic metastasis

From: Tumor metastasis to bone

Tumor-secreted factors Role in the pathogenesis of osteolytic metastasis
PTHrP Upregulates RANKL expression and decreases OPG expression [26,41]
Soluble RANKL Stimulates osteoclastogenesis by binding directly to RANK [43]
IL-6 Increases osteoclastogenesis via gp130 signal transduction pathway; enhances the effect of PTHrP [48]
IL-1 Increases osteoclastogenesis (RANKL dependent and independent pathway); promotes osteoclast activation and survival [78,79]
TNF-α Increases osteoclastogenesis and osteoclast activation (via gp130 signal transduction pathway as well as RANKL primed pathway) [80,81]
IL-8 Increases osteoclastogenesis by direct stimulation of CXCR1 receptors on the osteoclast precursor [47]
IL-11 Increases osteoclastogenesis via gp130 signal transduction pathway [48,82]
M-CSF Upregulates RANKL expression on stromal cells; chemotactic role for attracting osteoclasts to resorptive sites and prolongs survival of the mature osteoclast by inhibiting apoptosis [83]
TGF-β Inhibits osteoclast formation but can also directly stimulate osteoclast formation (in absence of RANKL) [49]
Prostaglandin Upregulates RANKL expression and enhances the effect of soluble RANKL [26,84]
VEGF Induces angiogenesis and promotes osteoclastogenesis [85]
MMPs Assist osteoclast mediated bone resorption [86]
  1. CXCR, C-X-C chemokine receptor; IL, interleukin; M-CSF, macrophage colony-stimulating factor; MMP, matrix metalloproteinase; OPG, osteoprotegerin; PTHrP, parathyroid hormone-related peptide; RANKL, receptor activator of nuclear factor-κB ligand; TGF, transforming growth factor; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.