Liu Gang, Zhang Jinyu, Frey Lewis, Gang Xiao, Wu Kongming, Liu Qian, Lilly Michael, Wu Jennifer
Department of Medicine, University of Washington, Seattle, WA, USA.
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA.
J Hematol Oncol. 2017 Jan 11;10(1):14. doi: 10.1186/s13045-016-0386-7.
The causative role of the pro-inflammatory cytokine IL-6 in prostate cancer progression has been well established at molecular level. However, whether and how IL-6 may play a role in prostate cancer risk and development is not well defined. One limitation factor to acquiring this knowledge is the lack of appropriate animal models.
We generated a novel line of prostate-specific IL-6 transgenic mouse model. We compared the prostate pathology, tumorigenic signaling components, and prostate tumor microenvironment of the IL-6 transgenic mice with wild type littermates.
With this model, we demonstrate that IL-6 induces prostate neoplasm autonomously. We further demonstrate that transgenic expression of IL-6 in the prostate activates oncogenic pathways, induces autocrine IL-6 secretion and steadily-state of STAT3 activation in the prostate tissue, upregulates paracrine insulin-like growth factor (IGF) signaling axis, reprograms prostate oncogenic gene expression, and more intriguingly, amplifies inflammation in the prostate and peri-prostatic adipose tissue.
The pro-inflammatory IL-6 is autonomous oncogene for the prostate. IL-6 induces prostate oncogenesis through amplifying local inflammation. We also presented a valuable animal model to study inflammation and prostate cancer development.
促炎细胞因子白细胞介素-6（IL-6）在前列腺癌进展中的致病作用已在分子水平上得到充分证实。然而，IL-6是否以及如何在前列腺癌风险和发展中发挥作用尚不清楚。获取这一知识的一个限制因素是缺乏合适的动物模型。
我们构建了一种新型的前列腺特异性IL-6转基因小鼠模型。我们将IL-6转基因小鼠与野生型同窝小鼠的前列腺病理学、致瘤信号成分和前列腺肿瘤微环境进行了比较。
利用该模型，我们证明IL-6可自主诱导前列腺肿瘤。我们进一步证明，前列腺中IL-6的转基因表达激活致癌途径，诱导自分泌IL-6分泌以及前列腺组织中STAT3激活的稳态，上调旁分泌胰岛素样生长因子（IGF）信号轴，重编程前列腺致癌基因表达，更有趣的是，放大前列腺和前列腺周围脂肪组织中的炎症。
促炎IL-6是前列腺的自主癌基因。IL-6通过放大局部炎症诱导前列腺肿瘤发生。我们还提供了一个有价值的动物模型来研究炎症和前列腺癌的发展。
