Bousset, Laura and Septier, Amandine and Bunay, Julio and Voisin, Allison and Guiton, Rachel and Damon-Soubeyrant, Christelle and Renaud, Yoan and De Haze, Angelique and Sapin, Vincent and Fogli, Anne and Rambur, Amandine and De Joussineau, Cyrille and Kocer, Ayhan and Trousson, Amalia and Henry-Berger, Joelle and Hoering, Marcus and Liebisch, Gerhard and Matysik, Silke and Lobaccaro, Jean-Marc A. and Morel, Laurent and Baron, Silvere (2020) Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia. PLOS BIOLOGY, 18 (12): e3000948. ISSN 1544-9173, 1545-7885
Full text not available from this repository. (Request a copy)Abstract
Chronic inflammation is now a well-known precursor for cancer development. Infectious prostatitis are the most common causes of prostate inflammation, but emerging evidence points the role of metabolic disorders as a potential source of cancer-related inflammation. Although the widely used treatment for prostate cancer based on androgen deprivation therapy (ADT) effectively decreases tumor size, it also causes profound alterations in immune tumor microenvironment within the prostate. Here, we demonstrate that prostates of a mouse model invalidated for nuclear receptors liver X receptors (LXRs), crucial lipid metabolism and inflammation integrators, respond in an unexpected way to androgen deprivation. Indeed, we observed profound alterations in immune cells composition, which was associated with chronic inflammation of the prostate. This was explained by the recruitment of phagocytosis-deficient macrophages leading to aberrant hyporesponse to castration. This phenotypic alteration was sufficient to allow prostatic neoplasia. Altogether, these data suggest that ADT and inflammation resulting from metabolic alterations interact to promote aberrant proliferation of epithelial prostate cells and development of neoplasia. This raises the question of the benefit of ADT for patients with metabolic disorders.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LIVER-X-RECEPTOR; METABOLIC SYNDROME; APOPTOTIC CELLS; OSTEOPONTIN EXPRESSION; PLASMA OSTEOPONTIN; CANCER; CASTRATION; INFLAMMATION; INFILTRATION; PROGRESSION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Mar 2021 07:11 |
| Last Modified: | 08 Mar 2021 07:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43288 |
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