AN INHIBITORY INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN (IN-IGFBP) FROM HUMAN PROSTATIC CELL CONDITIONED MEDIUM REVEALS N-TERMINAL SEQUENCE IDENTITY WITH BONE DERIVED IN-IGFBP

Abstract

Insulin-like growth factor binding proteins (IGFBPs), are produced by several cell types, are present in biological fluids, and may function in modulating insulin-like growth factor (IGF) biological activities. Recently the presence of multiple IGFBPs was reported in seminal fluid, suggesting that IGFBPs are produced by prostatic epithelium. We have found that human prostatic tumor cells of the PC3 cell line produce an IGFBP. PC3-IGFBP was purified to homogeneity using sequential IGF I affinity and HPLC C4 reverse phase chromatographies. Chemical cross-linking of PC3-IGFBP to 125I-IGF I revealed a molecular weight of 25 kDa. Its N-terminal sequence and amino-acid composition were highly homologous to that of a recently described 25 kDa inhibitory IGFBP (In-IGFBP), produced by osteoblasts in vitro. PC3-IGFBP inhibited basal and IGF II-stimulated bone cell DNA synthesis. We conclude that the PC3-IGFBP is very similar, if not identical to the osteoblast-derived In-IGFBP. Expression of PC3-IGFBP by metastatic human prostate tumor cells thus might affect the osteoblast proliferation that is induced by metastatic prostatic carcinoma. The PC3-IGFBP may be similar to a 24 kDa IGFBP described in seminal fluid and thus may be important in the regulation of cell proliferation in the male reproductive tract.