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Table 1 Factors in the metastatic bone microenvironment that effect osteolysis

From: Breast cancer metastasis to the bone: mechanisms of bone loss

Factor Source Target Effect on target Reference
PTH Serum OB ↑ RANKL [41]
PTHrP CC OB ↑ RANKL [13]
COX-2/PGE2 OB, CC OB, CC ↑ RANKL; in CC, ↑ MMPs [46, 47]
IL-1 Macrophages, monocytes, CC OB ↑ RANKL [41]
IL-11 OB OB ↑ RANKL [20]
TNFα Macrophages, EC OB ↑ RANKL [41]
IGF Serum OB ↑ RANKL [41]
FGF Stromal cells OB ↑ RANKL [41]
TGF-β OB, CC, matrix release OB, CC In OB, ↑ COX-2, cytokines; in CC, ↑ PTHrP [20]
PDGF OC, CC, platelets, megakaryocytes OB ↑ OB proliferation; ↓ OB differentiation; ↓ OB adhesion [58, 59]
Vitamin D/calcium Serum OB ↑ RANKL if deficient [66, 67]
Estrogen Serum OB, OC In OB, ↑ OPG production, ↑ collagen synthesis, ↓ cytokines, ↓ apoptosis; in OC, ↑ apoptosis [63, 64]
RANKL OB OC ↑ Osteoclastogenesis [13]
OPG OB OC ↓ Osteoclastogenesis [13]
IL-6 OB, CC OC ↑ Osteoclastogenesis [31]
IL-8 OB, CC, EC, monocytes OC ↑ OC activation [21]
M-CSF OB, CC OC ↑ Osteoclastogenesis [64]
MCP-1 OB, CC OC ↑ Osteoclastogenesis [22]
VEGF OB, CC, EC OC ↑ OC formation [48]
MMPs OB, CC, EC Matrix Matrix degradation [5]
Cathepsin K OC Matrix Matrix degradation [51]
  1. Up arrows indicate increase; down arrows indicate decrease. CC, cancer cell; EC, endothelial cell; FGF, fibroblast growth factor; IGF, insulin-like growth factor; MCP, monocyte chemotactic protein; M-CSF, macrophage colony-stimulating factor; MMP, matrix metalloproteinase; OB, osteoblast; OC, osteoclast; OPG, osteoprotegerin; PDGF, platelet-derived growth factor; PG, prostaglandin; PTH, parathyroid hormone; PTHrP, parathyroid hormone-related protein; RANK, receptor activator for NFκB; RANKL, receptor activator for NFκB ligand; TGF, transforming growth factor; VEGF, vascular endothelial growth factor.