title: Impact of prostate inflammation on lesion development in the POET3(+)Pten(+/-) mouse model of prostate carcinogenesis.
abstract: Evidence linking prostatitis and prostate cancer development is contradictory. To study this link, the POET3 mouse, an inducible model of prostatitis, was crossed with a Pten-loss model of prostate cancer (Pten(+/-)) containing the ROSA26 luciferase allele to monitor prostate size. Prostatitis was induced, and prostate bioluminescence was tracked over 12 months, with lesion development, inflammation, and cytokine expression analyzed at 4, 8, and 12 months and compared with mice without induction of prostatitis. Acute prostatitis led to more proliferative epithelium and enhanced bioluminescence. However, 4 months after initiation of prostatitis, mice with induced inflammation had lower grade pre-neoplastic lesions. A trend existed toward greater development of carcinoma 12 months after induction of inflammation, including one of two mice with carcinoma developing perineural invasion. Two of 18 mice at the later time points developed lesions with similarities to proliferative inflammatory atrophy, including one mouse with associated carcinoma. Pten(+/-) mice developed spontaneous inflammation, and prostatitis was similar among groups of mice at 8 and 12 months. Analyzed as one cohort, lesion number and grade were positively correlated with prostatitis. Specifically, amounts of CD11b(+)Gr1(+) cells were correlated with lesion development. These results support the hypothesis that myeloid-based inflammation is associated with lesion development in the murine prostate, and previous bouts of CD8-driven prostatitis may promote invasion in the Pten(+/-) model of cancer.
authors.affiliation: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana; Heeke Animal Disease Diagnostic Laboratory, Southern Indiana Purdue Agricultural Center, Dubois, Indiana.
authors.forename: Grant N
authors.initials: GN
authors.lastname: Burcham
authors.affiliation: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Cresswell
authors.affiliation: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana; Purdue University Center for Cancer Research, West Lafayette, Indiana.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Snyder
authors.affiliation: Department of Biochemistry, College of Agriculture, Purdue University, West Lafayette, Indiana.
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, College of Agriculture, Purdue University, West Lafayette, Indiana; Purdue University Center for Cancer Research, West Lafayette, Indiana.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana; Purdue University Center for Cancer Research, West Lafayette, Indiana.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Crist
authors.affiliation: Department of Physiology and Biophysics and Holden Comprehensive Cancer Center, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Henry
authors.affiliation: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana; Purdue University Center for Cancer Research, West Lafayette, Indiana. Electronic address: tlratliff@purdue.edu.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Ratliff
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D063646:Carcinogenesis; D049109:Cell Proliferation; D002469:Cell Separation; D018076:DNA, Complementary / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005434:Flow Cytometry; D005838:Genotype; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D049449:Luminescence; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011472:Prostatitis / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D018076:DNA, Complementary; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse