INHIBITION OF OSTEOBLASTIC CELL-DIFFERENTIATION BY CONDITIONED MEDIUMDERIVED FROM THE HUMAN PROSTATIC-CANCER CELL-LINE PC-3 IN-VITRO

Human prostatic carcinoma frequently metastasizes to bone tissue and a ctivates bone metabolism, especially bone formation, at the site of me tastasis. It has been reported that an extract of prostatic carcinoma and conditioned medium (CM) of a human prostatic carcinoma cell line, PC-3, established from a bone metastastic lesion, stimulate osteoblast ic cell proliferation. However, there is little information about the effect of PC-3 CM on the differentiation of osteoblastic cells. In thi s study, we investigated the effect of PC-3 CM on the differentiation of two types of osteoblastic cells, primary fetal rat calvaria (RC) ce lls containing many undifferentiated osteoprogenitor cells, and ROS 17 /2.8, a well-differentiated rat osteosarcoma cell line. PC-3 CM inhibi ted bone nodule formation and the activity of alkaline phosphatase (AL Pase), an osteoblastic marker enzyme, on days 7, 14, and 21 (RC cells) or 3, 6, and 9 (ROS 17/2.8 cells) in a dose-dependent manner (5-30% C M). However,, the CM did not affect cell proliferation or cell viabili ty. PC-3 CM was found to markedly block the gene expression of ALPase and osteocalcin (OCN) mRNAs but had no effect on the mRNA expression o f osteopontin (OPN), the latter two being noncollagenous proteins rela ted to bone matrix mineralization. These findings suggest that PC-3 CM contains a factor that inhibits osteoblastic cell differentiation and that this factor may be involved in the process of bone metastasis fr om prostatic carcinoma. (C) 1997 Wiley-Liss, Inc.