engleski

Expression of bone morphogenetic proteins in human prostate cancer with skeletal metastases

Prostatic adenocarcinoma is one of the most common cancers in men and preferentially metastasized to bone. Majority of skeletal metastases are osteoblastic in nature. These osteoblastic metastases show extensive new bone formation with possible involvement of the solubile growth factors such as bone morphogenetic proteins (BMPs)secreted by tumor cells. Bone morphogenetic proteins (BMPs) were originally extracted from bone as factors that induce cartilage and bone formation in vivo. They are multifunctional regulators of cell proliferation, differentiation and apoptosis. Human prostate cancer cells are known to produce several growth regulatory factors, including BMPs. The presence of BMPs in primary prostate carcinomas could be linked to the increased osteoblastic activity seen in skeletal metastasis. We investigated the expression of different BMPs in 25 histopathologically diagnosed prostate cancer samples. All examined patients had multiple skeletal metastases as shown by a positive bone scan. Tumor specimens were moderately or poorly differentiated cancer, according to the Gleason score. Paraffin-embeded samples were analyzed immunohistochemically using the polyclonal anti-BMP-2/4, -3, -5, -6, and -7 antibodies. The results demonstrated that adenocarcinoma specimens showed positive cytoplasmatic staining for BMP-2/4, -3, -5, and -6 in epithelial cancer cells. Also, we found BMP-7 positive nuclear staining. According to expression level of BMPs, BMP-2/4 is positive in 70-80% tumor cells, BMP-3 in 30-50% tumor cells, BMP-5 in 50-70% tumor cells and BMP-6 in 40-60% tumor cells. Our finding suggest that BMPs may hold potential role in prostate carcinoma pathogenesis and developing of skeletal metastasis.

prostate carcinoma; skeletal metastasis; bone morphogenetic proteins

DOI: 10.1007/s00223-003-5002-5