Table 1.Factors in the metastatic bone microenvironment that effect osteolysis

FactorSourceTargetEffect on TargetReferences
PTHSerumOB↑ RANKL61
PTHrPCCOB↑ RANKL62
Cox-2/PG-2OB, CCOB, CC↑ RANKL; in CC, ↑ MMPs63,64
IL-1Macrophages, monocytes, CCOB↑ RANKL61
L-11OBOB↑ RANKL65
TNFαMacrophages, ECOB↑ RANKL61
IGFSerumOB↑ RANKL61
FGFStromal cellsOB↑ RANKL61
TGF--βOB, CC, matrix releaseOB, CCIn OB,f Cox-2, cytokines; in CC, f PTHrP65
PDGFOC, CC, platelets, megakaryocytesOBf OB proliferation; -OB differentiation; -OB adhesion66,67
Vitamin D/ CalciumSerumOB↑ RANKL if deficient68,69
EstrogenSerumOB, OCIn OB,↑ OPG production,70,71
↑ collagen synthesis,
↓ cytokines, ↓ apoptosis;
in OC, ↑ apoptosis
RANKLOBOC↑ Osteoclastogenesis62
OPGOBOC↓ Osteoclastogenesis62
IL-6OB, CCOC↑ Osteoclastogenesis44
IL-8OB, CC, EC, monocytesOC↑ OC activation72
M-CSFOB,CCOC↑ Osteoclastogenesis71
MCP-1OB, CCOC↑ Osteoclastogenesis31
VEGFOB, CC, ECOC↑ OC formation73
MMPsOB, CC, ECMatrixMatrix degradation74
Cathepsin KOCMatrixMatrix degradation75

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, macrohphage colony-stimulating factor; MMP, matrix metalloproteinase; OB, osteoblast; OC, osteoclast; OPG, osteoprotegrin; 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. (Table adapted from Chen et al. Breast Cancer Res 2010, 12:215.34)

From: The Breast Cancer Metastases in Bone Conundrum

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