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Table 2 Pro-osteoblastic tumor-secreted factors and their described role in the establishment of osteoblastic metastasis

From: Tumor metastasis to bone

Tumor-secreted factors Probable mechanisms underlying new bone formation in osteoblastic metastases
Wnt Stimulates differentiation and activation, and promotes survival and activity of osteoblasts; inhibits osteoclast activity [52]
ET-1 Stimulates proliferation of osteoblasts, promotes mineralization, inhibits osteoclast motility, and potentiates the pro-osteogenic effects of other growth factors [59,60]
BMP Stimulates osteoblast proliferation, activity, and survival; increases OPG production [62-66]
IGF-1, IGF-2 Stimulate osteoblast proliferation and survival [87]
IL-6 Regulates osteoblast function [88]
OPG Inhibits osteoclastic activity by binding to RANKL [89]
TGF-β Stimulates osteoblast proliferation [90]
Urokinase (uPA) Stimulates osteoblast proliferation [91]
PDGF-BB Promotes angiogenesis and osteoblast activity [92]
FGF-1, FGF-2, and FGF-8 Promote differentiation and proliferation of osteoblasts [93]
PSA Inactivation of PTHrP and stimulation of latent growth factors (TGF-β) [94]
VEGF Promotes osteoblast differentiation [95]
MDA-BF-1 Stimulates osteoblast formation and activation [96]
  1. BMP, bone morphogenetic protein; ET, endothelin; FGF, fibroblast growth factor; IGF, insulin-like growth factor; OPG, osteoprotegerin; PDGF, platelet-derived growth factor; TGF, transforming growth factor; PSA, prostate-specific antigen; PTHrP, parathyroid hormone-related peptide; uPA, urokinase plasminogen activator; Wnt, wingless int; VEGF, vascular endothelial growth factor.