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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.