title: Pathogenic intestinal bacteria enhance prostate cancer development via systemic activation of immune cells in mice.
abstract: A role for microbes has been suspected in prostate cancer but difficult to confirm in human patients. We show here that a gastrointestinal (GI) tract bacterial infection is sufficient to enhance prostate intraepithelial neoplasia (PIN) and microinvasive carcinoma in a mouse model. We found that animals with a genetic predilection for dysregulation of wnt signaling, Apc (Min/+) mutant mice, were significantly susceptible to prostate cancer in an inflammation-dependent manner following infection with Helicobacter hepaticus. Further, early neoplasia observed in infected Apc (Min/+) mice was transmissible to uninfected mice by intraperitoneal injection of mesenteric lymph node (MLN) cells alone from H. hepaticus-infected mutant mice. Transmissibility of neoplasia was preventable by prior neutralization of inflammation using anti-TNF-α antibody in infected MLN donor mice. Taken together, these data confirm that systemic inflammation triggered by GI tract bacteria plays a pivotal role in tumorigenesis of the prostate gland.
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Theofilos
authors.initials: T
authors.lastname: Poutahidis
authors.forename: Kelsey
authors.initials: K
authors.lastname: Cappelle
authors.forename: Tatiana
authors.initials: T
authors.lastname: Levkovich
authors.forename: Chung-Wei
authors.initials: CW
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Doulberis
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Ge
authors.forename: James G
authors.initials: JG
authors.lastname: Fox
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Horwitz
authors.forename: Susan E
authors.initials: SE
authors.lastname: Erdman
mesh_terms: D000818:Animals; D017491:Genes, APC; D007422:Intestines / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000382:microbiology*