Interleukin-6: a multifunctional targetable cytokine in human prostate cancer.
Interleukin-6: a multifunctional targetable cytokine in human prostate cancer.
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DOI：
10.1016/j.mce.2011.05.033
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发表时间：
2012-09-05
影响因子：
4.1
通讯作者：
Puhr, Martin
中科院分区：
文献类型：
--
作者：
Culig, Zoran;Puhr, Martin
IL-6是一种多功能细胞因子，可调节前列腺癌的生长。IL-6刺激雄激素受体活性可增强或抑制增殖。IL-6抑制几种前列腺癌细胞系的凋亡。细胞因子信号转导抑制因子-3在前列腺癌中表达。在临床前研究和临床试验中测试了抗CNTO 328（抗IL-6）。几种细胞因子参与调节前列腺癌中的细胞事件。白细胞介素-6（IL-6）由于在疾病的早期阶段在癌组织中的表达增加而经常在前列腺癌模型中被研究。在转移性前列腺癌患者中，众所周知血清中IL-6水平升高。在对雄激素刺激无反应的细胞的上清液中测量到高水平的IL-6。前列腺癌中IL-6的表达增加是由于转化生长因子-β和活化蛋白-1复合物的成员的表达增强以及视网膜母细胞瘤肿瘤抑制因子的缺失。IL-6激活雄激素受体（AR）可能有助于前列腺癌亚组的进展。用两种前列腺癌细胞系LNCaP和MDA PCa 2b获得的结果表明，IL-6激活AR可能引起对增殖的刺激或抑制反应。有趣的是，IL-6长期治疗导致IL-6自分泌环的建立，抑制信号转导和转录激活因子（STAT）3的激活，并增加丝裂原活化蛋白激酶磷酸化。在几种细胞系中，IL-6通过激活磷脂酰肌醇3-激酶的信号传导途径作为存活分子。细胞因子信号传导抑制因子（SOCS）的表达在前列腺癌中已经被研究。SOCS-3阻止STAT 3的磷酸化，是AR阴性前列腺癌细胞中重要的抗凋亡因子。针对前列腺癌中IL-6的实验性治疗是基于使用单克隆抗体siltuximab，其可用于未来的个性化治疗。
► Interleukin-6 is a multifunctional cytokine which regulates growth of prostate cancer. ► Stimulation of androgen receptor activity by interleukin-6 may enhance or inhibit proliferation. ► Interleukin-6 inhibits apoptosis in several prostate cancer cell lines. ► Suppressor of cytokine signalling-3 is expressed in prostate cancer. ► Antibody CNTO 328 (Anti IL-6) was tested in preclinical research and clinical trials. Several cytokines are involved in regulation of cellular events in prostate cancer. Interleukin-6 (IL-6) was frequently investigated in prostate cancer models because of its increased expression in cancer tissue at early stages of the disease. In patients with metastatic prostate cancer, it is well-known that IL-6 levels increase in serum. High levels of IL-6 were measured in the supernatants of cells which do not respond to androgenic stimulation. IL-6 expression in prostate cancer increases due to enhanced expression of transforming growth factor-beta, and members of the activating protein-1 complex, and loss of the retinoblastoma tumour suppressor. IL-6 activation of androgen receptor (AR) may contribute to progression of a subgroup of prostate cancers. Results obtained with two prostate cancer cell lines, LNCaP and MDA PCa 2b, indicate that IL-6 activation of AR may cause either stimulatory or inhibitory responses on proliferation. Interestingly, prolonged treatment with IL-6 led to establishment of an IL-6 autocrine loop, suppressed signal transducer and activator of transcription (STAT)3 activation, and increased mitogen-activated protein kinase phosphorylation. In several cell lines IL-6 acts as a survival molecule through activation of the signalling pathway of phosphotidylinositol 3-kinase. Expression of suppressors of cytokine signalling (SOCS) has been studied in prostate cancer. SOCS-3 prevents phosphorylation of STAT3 and is an important anti-apoptotic factor in AR-negative prostate cancer cells. Experimental therapy against IL-6 in prostate cancer is based on the use of the monoclonal antibody siltuximab which may be used for personalised therapy coming in the future.
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影响因子：
82.9
作者：
Chen, CD;Welsbie, DS;Sawyers, CL
通讯作者：
Sawyers, CL
影响因子：
6
作者：
Bellezza, Ilaria;Neuwirt, Hannes;Culig, Zoran
通讯作者：
Culig, Zoran
DOI：
10.1073/pnas.92.16.7172
发表时间：
1995-08-01
影响因子：
11.1
作者：
GARRETT, KP;ASO, T;CONAWAY, JW
通讯作者：
CONAWAY, JW
影响因子：
50.3
作者：
Andersen, Raymond J.;Mawji, Nasrin R.;Sadar, Marianne D.
通讯作者：
Sadar, Marianne D.
影响因子：
6
作者：
Giri, D;Ozen, M;Ittmann, M
通讯作者：
Ittmann, M