Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia
| العنوان: | Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia |
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| المؤلفون: | Allison Voisin, Silvère Baron, Amandine Septier, Jean-Marc A. Lobaccaro, Ayhan Kocer, Gerhard Liebisch, Silke Matysik, Laura Bousset, Joelle Henry-Berger, Christelle Damon-Soubeyrant, Amandine Rambur, Vincent Sapin, Laurent Morel, Cyrille de Joussineau, Yoan Renaud, Julio Buñay, Amalia Trousson, Angélique De Haze, Marcus Höring, Rachel Guiton, Anne Fogli |
| المساهمون: | Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), University Hospital Regensburg, Génétique, Reproduction et Développement (GReD), Centre de Recherche en Nutrition Humaine Auvergne [CHU Clermont-Ferrand] (CRNH A), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Assuncao de Carvalho, Manuela |
| المصدر: | PLoS Biology PLoS Biology, 2020, 18 (12), pp.e3000948. ⟨10.1371/journal.pbio.3000948⟩ PLoS Biology, Public Library of Science, 2020, 18 (12), pp.e3000948. ⟨10.1371/journal.pbio.3000948⟩ PLoS Biology, Vol 18, Iss 12, p e3000948 (2020) |
| بيانات النشر: | HAL CCSD, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Physiology, [SDV]Life Sciences [q-bio], Receptors, Cytoplasmic and Nuclear, Apoptosis, Biochemistry, Androgen deprivation therapy, Prostate cancer, White Blood Cells, Mice, 0302 clinical medicine, Prostate, Animal Cells, Immune Physiology, Neoplasms, Medicine and Health Sciences, Tumor Microenvironment, Biology (General), Reproductive System Procedures, Immune Response, Liver X Receptors, Innate Immune System, Cell Death, General Neuroscience, Prostate Cancer, Prostate Diseases, 3. Good health, medicine.anatomical_structure, Oncology, Cell Processes, 030220 oncology & carcinogenesis, Androgens, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, Anatomy, Cellular Types, General Agricultural and Biological Sciences, Research Article, Mice, 129 Strain, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.drug_class, QH301-705.5, Urology, Immune Cells, Immunology, Prostatitis, Inflammation, Surgical and Invasive Medical Procedures, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Exocrine Glands, Signs and Symptoms, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Animals, Castration, Liver X receptor, Tumor microenvironment, Blood Cells, General Immunology and Microbiology, Macrophages, Immunity, Biology and Life Sciences, Cancers and Neoplasms, Prostatic Neoplasms, Androgen Antagonists, Cell Biology, Molecular Development, medicine.disease, Androgen, Hormones, Mice, Inbred C57BL, Genitourinary Tract Tumors, Disease Models, Animal, 030104 developmental biology, Immune System, Cancer research, Prostate Gland, Clinical Medicine, Developmental Biology |
| الوصف: | 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. Mice lacking the liver X nuclear receptors (LXRs), crucial integrators of lipid metabolism, were used to study the response of the prostate to androgen deprivation. This reveals that lack of androgens leads to chronic inflammation due to impaired clearance of castration-induced apoptotic cells, allowing production of pro-inflammatory cytokines and promoting prostate neoplasia. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1544-9173 1545-7885 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc4275bf1e4d5c2d81c2c4c719aecee3 https://hal.uca.fr/hal-03252478/document |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....dc4275bf1e4d5c2d81c2c4c719aecee3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15449173 15457885 |
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