Single-cell analyses unravel cell type–specific responses to a vitamin D analog in prostatic precancerous lesions
| Autor: | Justine Gantzer, Jean-Marc Bornert, Mohamed A. Abu el Maaty, Anna-Isavella Rerra, Elise Grelet, Gilles Laverny, Camille Emprou, Régis Lutzing, Julie Terzic, Céline Keime, Daniel Metzger |
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| Přispěvatelé: | Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), metzger, daniel |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine [SDV]Life Sciences [q-bio] Cell Diseases and Disorders vitamin D deficiency Extracellular matrix Mice 03 medical and health sciences Prostate cancer 0302 clinical medicine Tumor Microenvironment medicine Vitamin D and neurology Animals Humans PTEN Vitamin D Research Articles ComputingMilieux_MISCELLANEOUS Cancer Prostatic Intraepithelial Neoplasia Intraepithelial neoplasia Multidisciplinary biology business.industry SciAdv r-articles Prostatic Neoplasms medicine.disease 3. Good health [SDV] Life Sciences [q-bio] 030104 developmental biology medicine.anatomical_structure Apoptosis 030220 oncology & carcinogenesis biology.protein Cancer research Single-Cell Analysis business Precancerous Conditions Research Article |
| Zdroj: | Science Advances Science Advances, American Association for the Advancement of Science (AAAS), 2021, 7 (31), ⟨10.1126/sciadv.abg5982⟩ Science Advances, 2021, 7 (31), ⟨10.1126/sciadv.abg5982⟩ |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.abg5982⟩ |
| Popis: | Anti- and protumoral effects of a vitamin D analog revealed at single-cell resolution. Epidemiological data have linked vitamin D deficiency to the onset and severity of various cancers, including prostate cancer, and although in vitro studies have demonstrated anticancer activities for vitamin D, clinical trials provided conflicting results. To determine the impact of vitamin D signaling on prostatic precancerous lesions, we treated genetically engineered Pten(i)pe−/− mice harboring prostatic intraepithelial neoplasia (PIN) with Gemini-72, a vitamin D analog with reported anticancer activities. We show that this analog induces apoptosis in senescent PINs, normalizes extracellular matrix remodeling by stromal fibroblasts, and reduces the prostatic infiltration of immunosuppressive myeloid-derived suppressor cells. Moreover, single-cell RNA-sequencing analysis demonstrates that while a subset of luminal cells expressing Krt8, Krt4, and Tacstd2 (termed luminal-C cells) is lost by such a treatment, antiapoptotic pathways are induced in persistent luminal-C cells. Therefore, our findings delineate the distinct responses of PINs and the microenvironment to Gemini-72, and shed light on mechanisms that limit treatment’s efficacy. |
| Databáze: | OpenAIRE |
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