Breast cancer metastasis to the bone: mechanisms of bone loss

Breast Cancer Research

Table 1 Factors in the metastatic bone microenvironment that effect osteolysis

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]

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.

ISSN: 1465-542X