Inflammatory bowel disease induces inflammatory and pre-neoplastic changes in the prostate.
Prostate Cancer Prostatic Dis
; 25(3): 463-471, 2022 09.
Article
in En
| MEDLINE
| ID: mdl-34035460
ABSTRACT
BACKGROUND:
Inflammatory bowel disease (IBD) has been implicated as a risk factor for prostate cancer, however, the mechanism of how IBD leads to prostate tumorigenesis is not known. Here, we investigated whether chronic intestinal inflammation leads to pro-inflammatory changes associated with tumorigenesis in the prostate.METHODS:
Using clinical samples of men with IBD who underwent prostatectomy, we analyzed whether prostate tumors had differences in lymphocyte infiltrate compared to non-IBD controls. In a mouse model of chemically-induced intestinal inflammation, we investigated whether chronic intestinal inflammation could be transferred to the wild-type mouse prostate. In addition, mouse prostates were evaluated for activation of pro-oncogenic signaling and genomic instability.RESULTS:
A higher proportion of men with IBD had T and B lymphocyte infiltration within prostate tumors. Mice with chronic colitis showed significant increases in prostatic CD45 + leukocyte infiltration and elevation of three pro-inflammatory cytokines-TIMP-1, CCL5, and CXCL1 and activation of AKT and NF-kB signaling pathways. Lastly, mice with chronic colitis had greater prostatic oxidative stress/DNA damage, and prostate epithelial cells had undergone cell cycle arrest.CONCLUSIONS:
These data suggest chronic intestinal inflammation is associated with an inflammatory-rich, pro-tumorigenic prostatic phenotype which may explain how gut inflammation fosters prostate cancer development in men with IBD.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prostatic Neoplasms
/
Inflammatory Bowel Diseases
/
Colitis
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Prostate Cancer Prostatic Dis
Journal subject:
ENDOCRINOLOGIA
/
NEOPLASIAS
/
UROLOGIA
Year:
2022
Document type:
Article
Affiliation country:
United States
Country of publication:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM