RGD Reference Report - Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism. - Rat Genome Database

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Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism.

Authors: Dai, J  Keller, J  Zhang, J  Lu, Y  Yao, Z  Keller, ET 
Citation: Dai J, etal., Cancer Res. 2005 Sep 15;65(18):8274-85.
RGD ID: 2289018
Pubmed: PMID:16166304   (View Abstract at PubMed)
DOI: DOI:10.1158/0008-5472.CAN-05-1891   (Journal Full-text)

Prostate cancer frequently metastasizes to bone where it forms osteoblastic lesions through unknown mechanisms. Bone morphogenetic proteins (BMP) are mediators of skeletal formation. Prostate cancer produces a variety of BMPs, including BMP-6. We tested the hypothesis that BMP-6 contributes to prostate cancer-induced osteosclerosis at bone metastatic sites. Prostate cancer cells and clinical tissues produced BMP-6 that increased with aggressiveness of the tumor. Prostate cancer-conditioned medium induced SMAD phosphorylation in the preosteoblast MC3T3 cells, and phosphorylation was diminished by anti-BMP-6 antibody. Prostate cancer-conditioned medium induced mineralization of MC3T3 cells, which was blocked by both the BMP inhibitor noggin and anti-BMP-6. Human fetal bones were implanted in severe combined immunodeficient mice and after 4 weeks, LuCaP 23.1 prostate cancer cells were injected both s.c. and into the bone implants. Anti-BMP-6 or isotype antibody administration was then initiated. Anti-BMP-6 reduced LuCaP 23.1-induced osteoblastic activity, but had no effect on its osteolytic activity. This was associated with increased osteoblast numbers and osteoblast activity based on bone histomorphometric evaluation. As endothelin-1 has been implicated in bone metastases, we measured serum endothelin-1 levels but found they were not different among the treatment groups. In addition to decreased bone production, anti-BMP-6 reduced intraosseous, but not s.c., tumor size. We found that BMP-2, BMP-4, BMP-6, and BMP-7 had no direct effect on prostate cancer cell growth, but BMP-2 and BMP-6 increased the in vitro invasive ability of prostate cancer cell. These data show that prostate cancer promotes osteoblastic activity through BMP-6 and that, in addition to its bone effects, suggest that BMPs promote the ability of the prostate cancer cells to invade the bone microenvironment.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BMP6HumanNeoplasm Metastasis severityIMP associated with Prostatic Neoplasms and protein:increased expression:boneRGD 
Bmp6RatNeoplasm Metastasis severityISOBMP6 (Homo sapiens)associated with Prostatic Neoplasms and protein:increased expression:boneRGD 
Bmp6MouseNeoplasm Metastasis severityISOBMP6 (Homo sapiens)associated with Prostatic Neoplasms and protein:increased expression:boneRGD 

Objects Annotated

Genes (Rattus norvegicus)
Bmp6  (bone morphogenetic protein 6)

Genes (Mus musculus)
Bmp6  (bone morphogenetic protein 6)

Genes (Homo sapiens)
BMP6  (bone morphogenetic protein 6)


Additional Information