Hsu Yu-Hsiang, Wu Cheng-Ying, Hsing Chung-Hsi, Lai Wei-Ting, Wu Li-Wha, Chang Ming-Shi
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
PLoS One. 2015 Oct 6;10(10):e0139871. doi: 10.1371/journal.pone.0139871. eCollection 2015.
Interleukin (IL)-20 is a proinflammatory cytokine in the IL-10 family. IL-20 is associated with tumor promotion in the pathogenesis of oral, bladder, and breast cancer. However, little is known about the role of IL-20 in prostate cancer. We hypothesize that IL-20 promotes the growth of prostate cancer cells. Immunohistochemical staining showed that IL-20 and its receptors were expressed in human PC-3 and LNCaP prostate cancer cell lines and in prostate tumor tissue from 40 patients. In vitro, IL-20 upregulated N-cadherin, STAT3, vimentin, fibronectin, RANKL, cathepsin G, and cathepsin K, and increased the migration and colony formation of prostate cancer cells via activated p38, ERK1/2, AKT, and NF-κB signals in PC-3 cells. We investigated the effects of anti-IL-20 monoclonal antibody 7E on prostate tumor growth in vivo using SCID mouse subcutaneous and intratibial xenograft tumor models. In vivo, 7E reduced tumor growth, suppressed tumor-mediated osteolysis, and protected bone mineral density after intratibial injection of prostate cancer cells. We conclude that IL-20 is involved in the cell migration, colony formation, and tumor-induced osteolysis of prostate cancer. Therefore, IL-20 might be a novel target for treating prostate cancer.
白细胞介素(IL)-20是白细胞介素-10家族中的一种促炎细胞因子。在口腔癌、膀胱癌和乳腺癌的发病机制中,IL-20与肿瘤进展相关。然而,关于IL-20在前列腺癌中的作用知之甚少。我们推测IL-20促进前列腺癌细胞的生长。免疫组织化学染色显示,IL-20及其受体在人PC-3和LNCaP前列腺癌细胞系以及40例患者的前列腺肿瘤组织中表达。在体外,IL-20上调N-钙黏蛋白、信号转导和转录激活因子3(STAT3)、波形蛋白、纤连蛋白、核因子κB受体活化因子配体(RANKL)、组织蛋白酶G和组织蛋白酶K,并通过激活PC-3细胞中的p38、细胞外信号调节激酶1/2(ERK1/2)、蛋白激酶B(AKT)和核因子κB(NF-κB)信号增加前列腺癌细胞的迁移和集落形成。我们使用严重联合免疫缺陷(SCID)小鼠皮下和胫骨内异种移植瘤模型研究了抗IL-20单克隆抗体7E对体内前列腺肿瘤生长的影响。在体内,7E在胫骨内注射前列腺癌细胞后可减少肿瘤生长、抑制肿瘤介导的骨溶解并保护骨密度。我们得出结论,IL-20参与前列腺癌的细胞迁移、集落形成和肿瘤诱导的骨溶解。因此,IL-20可能是治疗前列腺癌的一个新靶点。