Culig Zoran, Steiner Hannes, Bartsch Georg, Hobisch Alfred
Department of Urology, Innsbruck Medical University, Innsbruck, Austria.
J Cell Biochem. 2005 Jun 1;95(3):497-505. doi: 10.1002/jcb.20477.
Interleukin-6 (IL-6) is involved in regulation of immune reaction and cell growth and differentiation. It causes multifunctional responses ranging from inhibition of proliferation to promotion of cell survival. IL-6 effects may depend on experimental conditions such as passage numbers and serum composition. IL-6 signals in target tissues through the receptor that is composed of the ligand-binding and signal-transducing subunits. IL-6 is expressed in benign and malignant prostate tissue and the levels of the cytokine and its receptor increase during prostate carcinogenesis. IL-6 is considered a positive growth factor for most prostate cells. The only exemption seems to be the LNCaP cell line, in which IL-6 causes growth arrest and induces differentiation function. In contrast, IL-6 acts as an autocrine growth factor in the subline LNCaP-IL-6+ established after chronic treatment with IL-6. IL-6 is a candidate for targeted therapy in prostate cancer because of its association with morbidity. Activation of signaling pathways of Janus kinase/signal transducers and activators of transcription factors, mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase has been reported in various prostate cancer cell lines. IL-6 and the related cytokine oncostatin M induce activation of the androgen receptor (AR) in the absence of androgen. IL-6 is also involved in regulation of vascular endothelial growth factor expression as well as neuroendocrine differentiation in prostate. Anti-IL-6 antibodies showed an inhibitory effect on the PC-3 xenograft. However, the development of this therapy in prostate cancer is in early stages.
白细胞介素-6（IL-6）参与免疫反应、细胞生长及分化的调节。它能引发从抑制增殖到促进细胞存活的多种功能反应。IL-6的作用可能取决于实验条件，如传代次数和血清成分。IL-6通过由配体结合亚基和信号转导亚基组成的受体在靶组织中发出信号。IL-6在良性和恶性前列腺组织中均有表达，且在前列腺癌发生过程中，该细胞因子及其受体的水平会升高。IL-6被认为是大多数前列腺细胞的正性生长因子。唯一的例外似乎是LNCaP细胞系，在该细胞系中IL-6会导致生长停滞并诱导分化功能。相反，在经IL-6长期处理后建立的亚系LNCaP-IL-6+中，IL-6作为自分泌生长因子发挥作用。由于IL-6与发病率相关，它是前列腺癌靶向治疗的一个候选靶点。在各种前列腺癌细胞系中均报道了Janus激酶/信号转导及转录激活因子、丝裂原活化蛋白激酶（MAPK）和磷脂酰肌醇3激酶信号通路的激活。在无雄激素的情况下，IL-6及相关细胞因子抑瘤素M可诱导雄激素受体（AR）的激活。IL-6还参与前列腺中血管内皮生长因子表达的调节以及神经内分泌分化。抗IL-6抗体对PC-3异种移植瘤显示出抑制作用。然而，这种前列腺癌治疗方法尚处于早期阶段。
