ECE2022 Poster Presentations Endocrine-Related Cancer (41 abstracts)
Znrf3 inactivation leads to a sexually dimorphic immune microenvironment in adrenocortical tumorigenesis
Julie Olabe 1 , Wilmouth James 2 , Basham Kaitlin 3 , Lucas Cecily 4 , Roucher-Boulez Florence 4 , Tauveron Igor 1 , Lefrancois-Martinez Anne-Marie 2 , Landwehr Laura-Sophie 5 , Kroiss Matthias 5 , Fassnacht Martin 5 , Hammer Gary 6 , Martinez Antoine 2 & Val Pierre 2
1Institut Génétique Reproduction et Développement Inserm UMR6293 - Centre Hospitalier Universitaire, Clermont-Ferrand, France; 2Institut Génétique Reproduction et Développement Inserm UMR6293, Clermont-Ferrand, France; 3University of Utah Hospital, Salt Lake City, United States; 4Hospices Civils de Lyon - Biochimie Biologie Moléculaire Grand Est - UM Pathologies Endocriniennes Rénales Musculaires et Mucoviscidose, Lyon, France; 5University Hospital, Würzburg, Germany; 6Departments of Internal Medicine (Metabolism, Endocrinology & Diabetes), Cell & Developmental Biology, and Molecular & Integrative Physiology - University of Michigan, Michigan, United States
Adrenocortical carcinoma (ACC) is a rare and aggressive cancer that originates from steroidogenic cells within the adrenal cortex. The most common alteration in ACC patients is inactivation of the transmembrane E3 ubiquitin-ligase Zinc and Ring Finger 3 (ZNRF3), which is responsible for inhibiting the canonical WNT/Beta-catenin pathway. Using Cre/loxP strategy, we showed that inactivation of Znrf3 in the adrenal cortex resulted in an initial hyperplasia by 6-weeks, after which sexually dimorphic phenotypes arose. We observed a senescent phenotype and a recruitment of macrophages with a higher phagocytic function in males, leading to regression of neoplastic cells and the absence of aggressive tumors in males. Moreover, androgen treatment of females inactivated for Znrf3 led to a reverse phenotype with regression. Interestingly, in patients, the incidence of ACC is higher in women. The analysis of histologic and genomic data of ACC patients reinforced the idea of a sexually dimorphic phenotype associated with phagocytic function and macrophages infiltration. Our current aim is to use this mouse model and patient data to highlight the role of macrophages in immunosurveillance and tumor inhibition within the adrenal cortex.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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