Document Detail

Prostate cancer cells and bone stromal cells mutually interact with each other through bone morphogenetic protein-mediated signals.
MedLine Citation:
PMID:  22532569     Owner:  NLM     Status:  MEDLINE    
Functional interactions between cancer cells and the bone microenvironment contribute to the development of bone metastasis. Although the bone metastasis of prostate cancer is characterized by increased ossification, the molecular mechanisms involved in this process are not fully understood. Here, the roles of bone morphogenetic proteins (BMPs) in the interactions between prostate cancer cells and bone stromal cells were investigated. In human prostate cancer LNCaP cells, BMP-4 induced the production of Sonic hedgehog (SHH) through a Smad-dependent pathway. In mouse stromal MC3T3-E1 cells, SHH up-regulated the expression of activin receptor IIB (ActR-IIB) and Smad1, which in turn enhanced BMP-responsive reporter activities in these cells. The combined stimulation with BMP-4 and SHH of MC3T3-E1 cells cooperatively induced the expression of osteoblastic markers, including alkaline phosphatase, bone sialoprotein, collagen type II α1, and osteocalcin. When MC3T3-E1 cells and LNCaP cells were co-cultured, the osteoblastic differentiation of MC3T3-E1 cells, which was induced by BMP-4, was accelerated by SHH from LNCaP cells. Furthermore, LNCaP cells and BMP-4 cooperatively induced the production of growth factors, including fibroblast growth factor (FGF)-2 and epidermal growth factor (EGF) in MC3T3-E1 cells, and these may promote the proliferation of LNCaP cells. Taken together, our findings suggest that BMPs provide favorable circumstances for the survival of prostate cancer cells and the differentiation of bone stromal cells in the bone microenvironment, possibly leading to the osteoblastic metastasis of prostate cancer.
Hikaru Nishimori; Shogo Ehata; Hiroshi I Suzuki; Yoko Katsuno; Kohei Miyazono
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-24
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-11     Completed Date:  2012-09-21     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  20037-46     Citation Subset:  IM    
Department of Molecular Pathology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
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MeSH Terms
Activin Receptors, Type II / genetics,  metabolism
Antigens, Differentiation / biosynthesis
Bone Morphogenetic Protein 4 / genetics,  metabolism*
Bone Neoplasms / genetics,  metabolism*,  pathology,  secondary
Calcinosis / genetics,  metabolism*,  pathology
Cell Line, Tumor
Epidermal Growth Factor / genetics,  metabolism
Fibroblast Growth Factor 2 / genetics,  metabolism
Neoplasm Proteins / genetics,  metabolism*
Osteoblasts / metabolism*,  pathology
Prostatic Neoplasms / genetics,  metabolism*,  pathology
Signal Transduction*
Smad1 Protein / genetics,  metabolism
Stromal Cells / metabolism,  pathology
Tumor Microenvironment*
Reg. No./Substance:
0/Antigens, Differentiation; 0/BMP4 protein, human; 0/Bmp4 protein, mouse; 0/Bone Morphogenetic Protein 4; 0/Neoplasm Proteins; 0/SMAD1 protein, human; 0/Smad1 Protein; 0/Smad1 protein, mouse; 103107-01-3/Fibroblast Growth Factor 2; 62229-50-9/Epidermal Growth Factor; EC Receptors, Type II; EC receptor type II-B

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