Table 1

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

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]


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.

Virk and Lieberman Arthritis Research & Therapy 2007 9(Suppl 1):S5   doi:10.1186/ar2169