Single-cell analyses unravel cell type-specific responses to a vitamin D analog in prostatic precancerous lesions.
Fiche publication
Date publication
juillet 2021
Journal
Science advances
Auteurs
Membres identifiés du Cancéropôle Est :
Dr METZGER Daniel, Dr LAVERNY Gilles, Dr GANTZER Justine
Tous les auteurs :
Abu El Maaty MA, Grelet E, Keime C, Rerra AI, Gantzer J, Emprou C, Terzic J, Lutzing R, Bornert JM, Laverny G, Metzger D
Lien Pubmed
Résumé
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 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.
Référence
Sci Adv. 2021 Jul;7(31):