Interleulin-17 Promotes Formation and Growth of Prostate Adenocarcinoma in Mouse Models
Menée sur divers modèles murins, cette étude met en évidence le rôle joué par l'interleukine 17 dans la formation et la croissance d'un adénocarcinome de la prostate
The contributions of interleukin-17 (IL-17) to cancer remain unclear and somewhat controversial. We took a genetic approach to explore its role in prostate cancers by interbreeding IL-17 receptor C (IL-17RC) deficient mice with mice that are conditionally mutant for PTEN, one established preclinical model for prostate cancer. Mice that were IL-17RC deficient (IL-17RC-) displayed prostates that were smaller than mice that maintained IL-17RC expression (IL-17RC+). Additionally, IL-17RC- mice developed a reduced number of invasive prostate adenocarcinomas with lower rates of cellular proliferation and higher apoptosis, compared to IL-17RC+ mice. Moreover, the fibromuscular stroma surrounding prostatic glands was relatively thicker in IL-17RC- mice and was associated with decreased Mmp7 expression and increased Timp1,2,4 expression, whereas administration of recombinant mouse IL-17 induced prostatic expression of Mmp7. Taken together, our results suggested that IL-17 promotes the formation and growth of prostate adenocarcinoma, and that an IL-17-MMP7 signaling axis is required for the transition of prostatic intraepithelial neoplasia (PIN) to frank adenocarcinoma.