Pathogenic Intestinal Bacteria Enhance Prostate Cancer Development via Systemic Activation of Immune Cells in Mice |
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Authors: | Theofilos Poutahidis Kelsey Cappelle Tatiana Levkovich Chung-Wei Lee Michael Doulberis Zhongming Ge James G. Fox Bruce H. Horwitz Susan E. Erdman |
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Affiliation: | 1. Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.; 2. Laboratory of Pathology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.; 3. Department of Immunopathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.; Northwestern University Feinberg School of Medicine, United States of America, |
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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, ApcMin/+ mutant mice, were significantly susceptible to prostate cancer in an inflammation-dependent manner following infection with Helicobacter hepaticus. Further, early neoplasia observed in infected ApcMin/+ 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. |
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