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Prostate-specific IL-6 transgene autonomously induce prostate neoplasm through amplifying inflammation in the prostate and peri-prostatic adipose tissue.
- Source :
-
Journal of hematology & oncology [J Hematol Oncol] 2017 Jan 11; Vol. 10 (1), pp. 14. Date of Electronic Publication: 2017 Jan 11. - Publication Year :
- 2017
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Adipose Tissue pathology
Animals
Cell Transformation, Neoplastic
Insulin-Like Growth Factor I metabolism
Interleukin-6 metabolism
Male
Mice
Mice, Transgenic
Oncogenes
Prostate pathology
Prostatic Neoplasms pathology
STAT3 Transcription Factor metabolism
Signal Transduction
Transgenes
Disease Models, Animal
Inflammation chemically induced
Interleukin-6 genetics
Prostatic Neoplasms chemically induced
Subjects
Details
- Language :
- English
- ISSN :
- 1756-8722
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of hematology & oncology
- Publication Type :
- Academic Journal
- Accession number :
- 28077171
- Full Text :
- https://doi.org/10.1186/s13045-016-0386-7