IGF BINDING PROTEIN-3 SECRETED BY THE PROSTATE ADENOCARCINOMA CELLS (PC-3) - DIFFERENTIAL EFFECT ON PC-3 AND NORMAL PROSTATE CELL-GROWTH

Deregulation of growth in malignant cells has been suggested to be the result of increased secretion by these cells, of autocrine growth fac tors; alternatively, this deregulation has been assumed to be related to loss of sensitivity by malignant cells to secreted inhibitory molec ules. The results of the present publication lend new support to both hypotheses. We recently showed that human prostate adenocarcinoma cell s (PC-3 cells) secreted insulin-like growth factor binding proteins (I GFBP) of 45, 34 and 25 kDa. From medium conditioned by dense cultures of PC-3 cells, we have now purified two IGFBPs of M(r) 45 kDa and 34 k Da. The N-amino terminal sequences were determined, and it was shown t hat they are IGFBP-3. IGFBP-34 appeared to be a deglycosylated form of IGFBP-45. The two IGFBPs had more affinity for IGF-II than for IGF-I. IGFBP-45 and IGFBP-34 were growth-inhibitory factors of chick embryo fibroblasts (CEF): they totally inhibited DNA synthesis stimulated by serum in CEF. Our results point to a clear difference between the effe cts of these IGFBPs upon growth of normal prostate cells and malignant PC-3 cells. At a concentration of 150 ng/ml, they inhibited growth of normal prostate cells even in the presence of 1 mug/ml insulin. This suggests that such inhibition was not simply the result of a decrease by the IGFBP of stimulation induced by serum IGF or IGF secreted by th e cells. At a concentration of 150 ng/ml, IGFBP did not modify the gro wth of PC-3 cells. In contrast, it stimulated growth of PC-3 cells whe n added at a concentration lower than 50 ng/ml (about 1 nM). Our resul ts thus provide new insight concerning the regulation of growth in PC- 3 cells.