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Comment
. 2007 Sep;171(3):739-43.
doi: 10.2353/ajpath.2007.070582. Epub 2007 Aug 9.

BMP7: a new bone metastases prevention?

Pierrick G J Fournier  1 , Theresa A Guise
Affiliations
Comment

BMP7: a new bone metastases prevention?

Pierrick G J Fournier et al. Am J Pathol. 2007 Sep.
No abstract available

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Figures

Figure 1
Figure 1
Role of BMP7 in prostate cancer progression and in bone metastases. Top: In the prostate gland, androgens stimulate the production of BMP7 by normal epithelial cells. Through Smad1/5/8, specifics of BMP signaling, BMP7 represses EMT via different mechanisms including the regulation of E-cadherin expression. BMP7, combined with TGF-β, which signals through Smad2/3, further increases E-cadherin expression and then more efficiently prevents EMT and cancer progression. In the later stage of the disease, BMP7 ceases to act on cancer cells, potentially because of the loss of androgen-induced production of BMP7 after anti-androgen therapy. TGF-β alone represses E-cadherin expression and favors EMT. Cancer cells then acquire a metastatic potential (metastable cells) and can disseminate through the bloodstream to other organs, including bones. Bottom: At sites of bone metastases, cancer cells produce osteolytic factors such as PTHrP, IL-8, or IL-11 that increase bone resorption by directly acting on osteoclasts and their precursors or via the osteoblasts through production of RANK ligand. Growth factors released from resorbed mineralized bone matrix, such as TGF-β, promote tumor growth in bone by enhancing the production of tumor factors that stimulate bone resorption and bone formation. Cancer cells can also induce osteoblast maturation and new bone formation by production of endothelin-1 (ET-1); platelet-derived growth factor (PDGF); and BMP4, -6, or -7. Mature osteoblasts secrete growth factors such as TGF-β that may fuel the progression of bone metastases. BMP7, used as a therapeutic agent, can inhibit TGF-β signaling and progression of this vicious cycle of tumor growth of bone metastases.
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