Prostate-specific IL-6 transgene autonomously induce prostate neoplasm through amplifying inflammation in the prostate and peri-prostatic adipose tissue.

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.

Journal of hematology & oncology. 2017 Jan 11*** epublish ***

Gang Liu, Jinyu Zhang, Lewis Frey, Xiao Gang, Kongming Wu, Qian Liu, Michael Lilly, Jennifer Wu

Department of Medicine, University of Washington, Seattle, WA, USA., Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA., Public Health Science, Medical University of South Carolina, Charleston, SC, 29425, USA., Department of Oncology, Tongji Medical College, Huazhong University of Science and Technology and Tongji Hospital, Wuhan, China., Department of Hematology and Oncology, Medical University of South Carolina, Charleston, SC, 29425, USA., Department of Medicine, University of Washington, Seattle, WA, USA. .