Autocrine regulation of cell proliferation by the insulin-like growth factor (IGF) and IGF binding protein-3 protease system in a human prostate carcinoma cell line (PC-3).
Autocrine regulation of cell proliferation by the insulin-like growth factor (IGF) and IGF binding protein-3 protease system in a human prostate carcinoma cell line (PC-3).
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人前列腺癌细胞系 (PC-3) 中胰岛素样生长因子 (IGF) 和 IGF 结合蛋白 3 蛋白酶系统对细胞增殖的自分泌调节。
DOI：
10.1210/endo.136.12.7588299
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发表时间：
1995
期刊：
影响因子：
4.8
通讯作者：
M. Binoux
中科院分区：
文献类型：
--
作者：
P. Angelloz;M. Binoux
PC-3细胞，其生长是雄激素非依赖性的，被证明能够在无血清培养基中缓慢增殖，并在没有添加生长因子的情况下持续7天。他们分泌胰岛素样生长因子（IGF）-II，但没有检测到IGF-I。这种IGF-II，虽然少量产生，但在其增殖中起作用，因为在针对IGF或1型IGF受体的单克隆抗体存在下，生长可剂量依赖性地抑制高达80%。PC-3细胞还分泌IGF结合蛋白（IGFBPs）-2、-3、-4和-6。免疫印迹分析显示IGFBP-3的选择性蛋白水解，产生与体内IGFBP-3产生的分子大小相同的片段。通过向培养基中添加对细胞无毒的浓度<0.2mM的丝氨酸蛋白酶抑制剂4-（2-氨基乙基）-苯磺酰氟（Pefabloc-SC），细胞增殖被剂量依赖性地抑制高达80%，同时，细胞分泌的IGFBP-3的蛋白水解被抑制。在条件培养基中检测到的尿激酶活性被Pefabloc抑制，表明尿激酶型纤溶酶原激活剂参与IGFBP-3的蛋白水解。此外，0.01-5微克/毫升纤溶酶原诱导培养基中增殖和蛋白水解的IGFBP-3比例的剂量依赖性增加。在抗1型IGF受体抗体的存在下，增殖的刺激被完全阻断。将重组人IGF-II（5-200 ng/ml）加入到通过48 h培养物调节的无细胞培养基中，剂量依赖性地刺激PC-3细胞增殖。在浓度≤ 100 ng/ml时，当培养基由在纤溶酶原存在下培养的细胞调节时，其促有丝分裂作用增强，但当培养基由在Pefabloc存在下培养的细胞调节时，其促有丝分裂作用受到抑制。我们从这些结果中得出结论：1）IGF-II通过1型IGF受体参与PC-3细胞增殖的自分泌控制; 2）这种增殖直接依赖于IGF-II的生物利用度，而IGF-II的生物利用度本身受尿激酶型纤溶酶原激活物和纤溶酶诱导的有限IGFBP-3蛋白水解的调节，至少部分是由尿激酶型纤溶酶原激活物和纤溶酶诱导的。
PC-3 cells, whose growth is androgen-independent, were shown to be capable of slow proliferation in serum-free medium and in the absence of added growth factor for 7 days. They secreted insulin-like growth factor (IGF)-II but no detectable IGF-I. This IGF-II, although produced in small amounts, plays a role in their proliferation because growth could be inhibited dose dependently by up to 80% in the presence of monoclonal antibodies directed against IGFs or the type 1 IGF receptor. PC-3 cells also secreted IGF binding proteins (IGFBPs) -2, -3, -4, and -6. Immunoblot analysis revealed selective proteolysis of IGFBP-3, yielding fragments of the same molecular size as those generated from IGFBP-3 in vivo. With the addition to the culture medium of a serine protease inhibitor, 4-(2-aminoethyl)-benzenesulfonyl fluoride (Pefabloc-SC), at concentrations < 0.2 mM that were nontoxic to the cells, cell proliferation was dose dependently inhibited up to 80% and, at the same time, proteolysis of the IGFBP-3 secreted by the cells was depressed. Urokinase activity detected in the conditioned media was depressed by Pefabloc, suggesting that the urokinase-type plasminogen activator was involved in the proteolysis of IGFBP-3. In addition, 0.01-5 micrograms/ml plasminogen induced a dose-dependent increase in both proliferation and the proportions of proteolysed IGFBP-3 in the media. The stimulation of proliferation was totally blocked in the presence of anti-type 1 IGF receptor antibody. Recombinant human IGF-II (5-200 ng/ml) added to cell-free medium conditioned by 48 h of culture dose dependently stimulated PC-3 cell proliferation. At concentrations < or = 100 ng/ml, its mitogenic action was potentiated when medium had been conditioned by cells cultured in the presence of plasminogen but inhibited when medium had been conditioned by cells cultured in the presence of Pefabloc. We conclude from these results 1) that IGF-II is involved in the autocrine control of PC-3 cell proliferation via the type 1 IGF receptor; and 2) that this proliferation is directly dependent on IGF-II bioavailability that itself is modulated by the limited IGFBP-3 proteolysis induced, at least in part, by urokinase-type plasminogen activator and plasmin.
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影响因子：
5.8
作者：
COHEN, P;PEEHL, DM;ROSENFELD, RG
通讯作者：
ROSENFELD, RG
IGFBP-3 的蛋白水解可能是体内 IGF 作用的常见调节机制。
DOI：
--
发表时间：
1993
期刊：
Growth regulation
影响因子：
--
作者：
Lamson,G;Giudice,LC;Cohen,P;Liu,F;Gargosky,S;Muller,HL;Oh,Y;Wilson,KF;Hintz,RL;Rosenfeld,RG
通讯作者：
Rosenfeld,RG
人前列腺上皮细胞和基质成纤维细胞培养物的胰岛素样生长因子结合蛋白 3 表达和分泌。
DOI：
10.1677/joe.0.1410535
发表时间：
1994
期刊：
The Journal of endocrinology
影响因子：
--
作者：
Birnbaum,RS;Ware,JL;Plymate,SR
通讯作者：
Plymate,SR
可释放纤溶酶原激活剂的比色测定。
影响因子：
9.3
作者：
Campbell,EE;Shifman,MA;Lewis,JG;Pasqua,JJ;Pizzo,SV
通讯作者：
Pizzo,SV
人体生物体液中胰岛素样生长因子结合蛋白 3 的测量和表征：放射免疫测定法和配体印迹之间的差异。
影响因子：
4.8
作者：
Gargosky,SE;Pham,HM;Wilson,KF;Liu,F;Giudice,LC;Rosenfeld,RG
通讯作者：
Rosenfeld,RG