title: Targeting Th17-IL-17 Pathway in Prevention of Micro-Invasive Prostate Cancer in a Mouse Model.
abstract: BACKGROUND
  Chronic inflammation has been associated with the development and progression of human cancers including prostate cancer. The exact role of the inflammatory Th17-IL-17 pathway in prostate cancer remains unknown. In this study, we aimed to determine the importance of Th17 cells and IL-17 in a Pten-null prostate cancer mouse model.
  
  
  METHODS
  The Pten-null mice were treated by Th17 inhibitor SR1001 or anti-mouse IL-17 monoclonal antibody from 6 weeks of age up to 12 weeks of age. For SR1001 treatment, the mice were injected intraperitoneally (i.p.) twice a day with vehicle or SR1001, which was dissolved in a dimethylsulfoxide (DMSO) solution. All mice were euthanized for necropsy at 12 weeks of age. For IL-17 antibody treatment, the mice were injected intravenously (i.v.) once every two weeks with control IgG or rat anti-mouse IL-17 monoclonal antibody, which was dissolved in PBS. The injection time points were at 6, 8, and 10 weeks old. All mice were analyzed for the prostate phenotypes at 12 weeks of age.
  
  
  RESULTS
  We found that either SR1001 or anti-IL-17 antibody treatment decreased the formation of micro-invasive prostate cancer in Pten-null mice. The SR1001 or anti-IL-17 antibody treated mouse prostates had reduced proliferation, increased apoptosis, and reduced angiogenesis, as well as reduced inflammatory cell infiltration. By assessing the epithelial-to-mesenchymal transition (EMT) markers, we found that SR1001 or anti-IL-17 antibody treated prostate tissues had weaker EMT phenotype compared to the control treated prostates.
  
  
  CONCLUSIONS
  These results demonstrated that Th17-IL-17 pathway plays a key role in prostate cancer progression in Pten-null mice. Targeting Th17-IL-17 pathway could prevent micro-invasive prostate cancer formation in mice. Prostate 77:888-899, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Structural & Cellular Biology, Tulane University, New Orleans, Louisiana.|Tulane Center for Aging, Tulane University, New Orleans, Louisiana.
authors.forename: Qiuyang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Structural & Cellular Biology, Tulane University, New Orleans, Louisiana.
authors.forename: Sen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Structural & Cellular Biology, Tulane University, New Orleans, Louisiana.
authors.forename: Dongxia
authors.initials: D
authors.lastname: Ge
authors.affiliation: Department of Structural & Cellular Biology, Tulane University, New Orleans, Louisiana.
authors.forename: David M
authors.initials: DM
authors.lastname: Cunningham
authors.affiliation: Department of Structural & Cellular Biology, Tulane University, New Orleans, Louisiana.|Department of Clinical Medicine, The First Affiliated Hospital, Shaanxi University of Chinese Medicine, Xianyang, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Structural & Cellular Biology, Tulane University, New Orleans, Louisiana.|Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, Missouri.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Burris
authors.affiliation: Department of Structural & Cellular Biology, Tulane University, New Orleans, Louisiana.|Tulane Center for Aging, Tulane University, New Orleans, Louisiana.|Department of Orthopaedic Surgery, Tulane University, New Orleans, Louisiana.|Tulane Cancer Center and Louisiana Cancer Research Consortium, Tulane University, New Orleans, Louisiana.|Tulane Center for Stem Cell Research and Regenerative Medicine, Tulane University, New Orleans, Louisiana.
authors.forename: Zongbing
authors.initials: Z
authors.lastname: You
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004195:Disease Models, Animal; D016903:Drug Monitoring / Q000379:methods; D007155:Immunologic Factors / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology*; D007274:Injections, Intraperitoneal; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000276:immunology; D008297:Male; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control; D011467:Prostate / Q000276:immunology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology*; D058504:Th17 Cells / Q000276:immunology*; D013844:Thiazoles / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D020381:Interleukin-17; C558809:SR1001; D013449:Sulfonamides; D013844:Thiazoles
keywords: Pten-null mice; SR1001; Th17-IL-17 pathway; anti-IL-17 antibody; prostate cancer