BMP4 promotes prostate tumor growth in bone through osteogenesis - Abstract

Molecular pathology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, United States.

 

Induction of new bone formation is frequently seen in the bone lesions from prostate cancer (PCa). However, whether osteogenesis is necessary for prostate tumor growth in bone is unknown. Recently, two xenografts, MDA-PCa-118b and MDA-PCa-133, were generated from PCa bone metastases. When implanted subcutaneously in SCID mice, MDA-PCa-118b induced strong ectopic bone formation while MDA-PCa-133 did not. To identify the factors that are involved in bone formation, we compared the expression of secreted factors ("secretome") from MDA-PCa-118b and MDA-PCa-133 by cytokine array. We found that the osteogenic MDA-PCa-118b xenograft expressed higher levels of BMP-4 and several cytokines including IL-8, Gro, and CCL2. We demonstrated that BMP-4 secreted from MDA-PCa-118b contributed to about a third of the osteogenic differentiation seen in MDA-PCa-118b tumors. The conditioned media from MDA-PCa-118b induced a higher level of osteoblast differentiation, which was significantly reduced by treating with BMP-4 neutralizing antibody or the small molecule BMP receptor 1 inhibitor LDN-193189. BMP-4 did not elicit an autocrine effect on MDA-PCa-118b, which expressed low to undetectable levels of BMP receptors. Treatment of SCID mice bearing MDA-PCa-118b tumors with LDN-193189 significantly reduced tumor growth. Thus, these studies support a role of BMP4-mediated osteogenesis in the progression of PCa in bone.

Written by:
Lee YC, Cheng CJ, Bilen MA, Lu JF, Satcher RL, Yu-Lee LY, Gallick GE, Maity SN, Lin SH.   Are you the author?

Reference: Cancer Res. 2011 Jun 13. Epub ahead of print.
doi: 10.1158/0008-5472.CAN-10-4374

PubMed Abstract
PMID: 21670081

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