BONE MORPHOGENETIC PROTEIN-6 IN SKELETAL METASTASES FROM PROSTATE-CANCER AND OTHER COMMON HUMAN MALIGNANCIES

Prostatic adenocarcinoma Commonly metastasizes to bone. Unlike most ot her bony secondaries, the majority of skeletal prostatic metastases ar e osteoblastic rather than osteolytic in nature. Several growth factor s which are known to stimulate bone formation are expressed in benign and malignant prostate cells, but none has been specifically linked to osteosclerotic metastases. Bone morphogenetic proteins (BMPs) induce ectopic bone formation in vivo. We have reported previously that BMP-6 mRNA and protein are expressed in the majority of primary prostatic c arcinomas with established skeletal metastases but rarely in clinicall y organ-Confined tumours. This study examines the expression of BMP-B mRNA in matched prostatic primary and secondary bony lesions and in is olated skeletal metastases from prostatic adenocarcinomas, as well as other common human malignancies, by in situ hybridization. BMP-6 mRNA was detected in 11 out of 13 bone metastases from prostate carcinoma a nd in three paired samples of primary prostate carcinoma and matching skeletal metastasis. Weak signals for BMP-B were also present in 5 out of 17 skeletal deposits from non-prostatic malignancies; BMP-B mRNA a ppears to be strongly expressed in prostatic adenocarcinomas, both in the primary tumour and in bone metastases. It is also expressed, thoug h less frequently, in skeletal metastases from other human carcinomas. Our findings suggest that BMP-6 may hold potential as an attractive m arker and possible mediator of skeletal metastases, particularly in pr ostate carcinoma.