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Allied Journal of Medical Research
|
Volume 2
Page 21
Note:
allied
academies
CANCER THERAPY AND ONCOLOGY
NEUROLOGY AND BRAIN DISORDERS
&
International Conference on
International Conference on
J u n e 2 1 - 2 2 , 2 0 1 8 | O s a k a , J a p a n
Joint Event on
IL-17-MMP7-EMT AXIS AS POTENTIAL
DRUGGABLE TARGET IN THE PREVENTION
AND TREATMENT OF PROSTATE CANCER
Zongbing You
Tulane University School of Medicine, USA
T
h17 cells are a subset of T helper cells secreting interleukin-17
(IL-17A and IL-17F). We have systematically investigated the role
of IL-17 in prostate cancer. We found that IL-17 receptor C (IL-17RC)
expression was up-regulated in human prostatic intraepithelial neoplasia
(PIN), hormone naïve prostate cancer, and castration-resistant prostate
cancer. Using an Il-17rc;Pten (Phosphatase and tensin homolog) double
knockout mouse model, we found that IL-17 promoted development of
hormone- naïve and castration-resistant prostate cancer through multiple
mechanisms, including: 1) directly stimulating expression of cytokines,
chemokines, and growth factors; 2) directly inducing inflammatory cell
infiltration; 3) increasing the ratio of immunosuppressive immune cells;
4) increasing angiogenesis; 5) enhancing cellular proliferation; and 6)
inhibiting cellular apoptosis. Using an Mmp7;Pten double knockout
mouse model, we found that MMP7 promoted prostate adenocarcinoma
through induction of epithelial-to-mesenchymal transition (EMT). IL-17
induced MMP7 and EMT in human prostate cancer cell lines, while siRNA
knockdown of MMP7 inhibited IL-17-induced EMT. Selective inhibitor of
MMP7, inhibitor of Th17 cell differentiation, and anti-IL-17A neutralizing
antibodies were able to partially inhibit prostate cancer formation in the
Pten knockout mice. These findings demonstrate that IL-17-MMP7- EMT
axis plays an important role in prostate cancer development, indicating
IL-17-MMP7-EMT axis as a potential target for developing new strategies
in the prevention and treatment of prostate cancer.
Zongbing You received his MD at the age of 23
years and PhD at the age of 28 years fromWest
China University of Medical Sciences, Chengdu,
China. He is a tenured Associate Professor and
Vice Chair for Research as well as Director of the
Two-Year Research Master’s Degree Program in
the Department of Structural and Cellular Biolo-
gy at Tulane University School of Medicine, New
Orleans, Louisiana, USA. He has published 80
publications and edited a professional book. His
research interest is in inflammation and pros-
tate cancer.
zyou@tulane.eduBIOGRAPHY
Zongbing You, Allied J Med Res 2018, Volume 2