The Aged Microenvironment Influences Prostate Carcinogenesis

The most important single risk factor associated with prostate cancer is advanced age. Despite the strong correlation between aging and prostate cancer, the mechanism(s) underlying this relationship remains unknown. In this study, we quantitated histological and molecular alterations of the mouse pr...

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Bibliographic Details
Main Author: Bianchi-Frias, Daniella
Format: Report
Language:English
Subjects:
AGING(PHYSIOLOGY)
Anatomy and Physiology
COLLAGEN
ENRICHMENT
GENOTOXICITY
HISTOCHEMISTRY
IMMUNOCHEMISTRY
IN VIVO ANALYSIS
INFLAMMATION
Medicine and Medical Research
MICE
ONCOGENESIS
PROSTATE CANCER
PROSTATE GLAND
RISK
STRESS(PHYSIOLOGY)
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Summary:The most important single risk factor associated with prostate cancer is advanced age. Despite the strong correlation between aging and prostate cancer, the mechanism(s) underlying this relationship remains unknown. In this study, we quantitated histological and molecular alterations of the mouse prostatic stroma that associate with normal aging in vivo. In a comparison of young (4 month) and old (20-24 month) mice, we identified significant changes in the expression of 1259 genes (p0.05) in the prostatic stroma that associated with normal aging in vivo. These included over-expression of genes associated with inflammation (e.g., Ccl8, Ccl12), genotoxic/oxidative stress (e.g., Apod, Serpinb5) and soluble factors (e.g., Cyr61) and, down-regulation of pro-collagen genes (e.g., Col1a1 and Col3a1). We demonstrated that aged prostates exhibit a disrupted collegenous matrix and aged collagen induced the invasion of prostate cancer cells in vitro. Immunohistochemical studies revealed an enrichment of inflammatory cells in aged prostates. Together, these findings demonstrated that during normal aging the prostate exhibits phenotypic and molecular characteristics that are also associated with malignancies. The original document contains color images.