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Skeletal metastases are common in advanced prostate cancer, causing considerable morbidity, and they are usually osteoblastic in nature with no clear explanation for this phenomenon. Bone morphogenetic proteins (BMPs) induce bone formation in vivo, and preliminary work showed a possible association between BMPs and prostatic skeletal metastases; differential expression favors BMP-6 as a potential new marker and mediator of osteosclerotic deposit formation. We investigated BMP-6 mRNA and protein expression by in situ hybridization and immunohistochemistry in malignant and benign prostates from 40 men. BMP-6 mRNA expression was detected exclusively in malignant epithelial cells in 20 of 21 patients (95%) with metastases and in 2 of 11 patients (18%) with localized cancer, and it was absent in 8 benign samples. Immunostaining for BMP-6 was predominantly cytoplasmic and was present in all primary tumors with established metastases and in 4 of 11 (36%) organ-confined cancers. In benign prostatic hyperplasia, basal cells and areas of basal cell hyperplasia were positive for BMP-6 by immunohistochemistry. The results suggest a close association between BMP-6 expression in primary malignant prostatic tissue and skeletal metastases. BMP-6 may be responsible, in part, for the osteoblastic changes in metastatic lesions secondary to prostate cancer.

Type

Journal article

Journal

Cancer Res

Publication Date

01/10/1997

Volume

57

Pages

4427 - 4431

Keywords

Adenocarcinoma, Biomarkers, Tumor, Blotting, Western, Bone Morphogenetic Protein 6, Bone Morphogenetic Proteins, Bone Neoplasms, Cytoplasm, Epithelium, Humans, Immunoenzyme Techniques, In Situ Hybridization, Male, Neoplasm Proteins, Prostate, Prostatic Hyperplasia, Prostatic Neoplasms, RNA, Messenger