A human prostatic bacterial isolate alters the prostatic microenvironment and accelerates prostate cancer progression

Area of Science:

• Urology
• Oncology
• Microbiology

Background:

• Inflammation is linked to prostate diseases like benign enlargement and cancer, but a direct causal role remains unproven.
• Understanding the prostate's inflammatory microenvironment is crucial for deciphering disease progression.

Purpose of the Study:

• To investigate the prostate inflammatory microenvironment following infection with a specific bacterial strain.
• To determine how this inflammation impacts prostate cancer progression.

Main Methods:

• Mimicked human prostate infection using retrograde urethral instillation of *Escherichia coli* (CP1).
• Analyzed inflammatory responses, epithelial and stromal changes, and immune cell infiltration (macrophages, Th17 cells) via flow cytometry.
• Assessed cytokine profiles and cancer development in the Hi-Myc mouse model.

Main Results:

• CP1 infection induced acute and chronic prostate inflammation, epithelial/stromal hyperplasia, and persistent inflammatory cell infiltrates.
• Inflammation led to persistent epithelial proliferation despite reduced androgen receptor (AR) expression.
• CP1 infection accelerated invasive prostate adenocarcinoma development in the Hi-Myc model, with 70% more mice developing cancer.

Conclusions:

• Prostate inflammation directly accelerates prostate cancer progression.
• Specific inflammatory cytokines are altered during concurrent inflammation and cancer.
• The study provides evidence for microenvironmental changes driven by inflammation that promote tumor initiation and progression.