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J Hematol Oncol. 2017 Jan 11;10(1):14. doi: 10.1186/s13045-016-0386-7.

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

Author information

1
Department of Medicine, University of Washington, Seattle, WA, USA.
2
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA.
3
Public Health Science, Medical University of South Carolina, Charleston, SC, 29425, USA.
4
Present address: Department of Laboratory Medicine, The Third Hospital of South Medical University, Guangzhou, China.
5
Department of Oncology, Tongji Medical College, Huazhong University of Science and Technology and Tongji Hospital, Wuhan, China.
6
Department of Hematology and Oncology, Medical University of South Carolina, Charleston, SC, 29425, USA.
7
Department of Medicine, University of Washington, Seattle, WA, USA. wujjd@musc.edu.
8
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA. wujjd@musc.edu.
9
Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA. wujjd@musc.edu.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

IL-6; Inflammation; Prostate neoplasm; Transgenic mouse

PMID:
28077171
PMCID:
PMC5225646
DOI:
10.1186/s13045-016-0386-7
[Indexed for MEDLINE]
Free PMC Article

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