IGF binding protein-3 secreted by the prostate adenocarcinoma cells (PC-3): differential effect on PC-3 and normal prostate cell growth.
IGF binding protein-3 secreted by the prostate adenocarcinoma cells (PC-3): differential effect on PC-3 and normal prostate cell growth.
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前列腺腺癌细胞 (PC-3) 分泌的 IGF 结合蛋白 3：对 PC-3 和正常前列腺细胞生长的不同影响。
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发表时间：
1993
期刊：
影响因子：
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通讯作者：
L. Harel
中科院分区：
文献类型：
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作者：
E. Kaicer;C. Blat;J. Imbenotte;F. Troalen;O. Cussenot;F. Calvo;L. Harel
恶性细胞的生长失调被认为是这些细胞分泌自分泌生长因子增加的结果；另外，这种解除管制被认为与恶性细胞对分泌的抑制分子失去敏感性有关。本出版物的结果为这两种假设提供了新的支持。我们最近发现，人前列腺腺癌细胞（PC-3细胞）分泌45、34和25 kDa的胰岛素样生长因子结合蛋白（IGFBP）。从PC-3细胞密集培养的培养基中，我们现在纯化了两个M(r) 45 kDa和34 kDa的igfbp。经n -氨基末端序列测定，表明其为IGFBP-3。IGFBP-34似乎是IGFBP-45的去糖基化形式。这两种igfbp对IGF-II的亲和力大于对IGF-I的亲和力。IGFBP-45和IGFBP-34是鸡胚成纤维细胞（CEF）的生长抑制因子，能完全抑制血清对CEF的DNA合成。我们的研究结果表明，这些igfbp对正常前列腺细胞和恶性PC-3细胞生长的影响存在明显差异。当浓度为150 ng/ml时，即使胰岛素浓度为1微克/毫升，它们也能抑制正常前列腺细胞的生长。这表明，这种抑制不仅仅是由于血清IGF或细胞分泌的IGF诱导的IGFBP刺激减少的结果。在浓度为150 ng/ml时，IGFBP对PC-3细胞的生长没有影响。相反，当浓度低于50 ng/ml（约1 nM）时，对PC-3细胞的生长有促进作用。因此，我们的研究结果为PC-3细胞的生长调控提供了新的见解。
Deregulation of growth in malignant cells has been suggested to be the result of increased secretion by these cells, of autocrine growth factors; alternatively, this deregulation has been assumed to be related to loss of sensitivity by malignant cells to secreted inhibitory molecules. The results of the present publication lend new support to both hypotheses. We recently showed that human prostate adenocarcinoma cells (PC-3 cells) secreted insulin-like growth factor binding proteins (IGFBP) 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 kDa. The N-amino terminal sequences were determined, and it was shown that 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 effects 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 microgram/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 the cells. At a concentration of 150 ng/ml, IGFBP did not modify the growth of PC-3 cells. In contrast, it stimulated growth of PC-3 cells when added at a concentration lower than 50 ng/ml (about 1 nM). Our results thus provide new insight concerning the regulation of growth in PC-3 cells.