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] |