Dlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma

作者：Katia Mariniello, James Pittaway, Barbara Altieri, Kleiton Silva Borges, Irene Hadjidemetriou, Claudio Henrique T. Ribeiro, Gerard Ruiz‐Babot, David S. Tourigny, Jiang A. Lim, Julie Foster, Julie Cleaver, Jane Sosabowski, Nafis A. Rahman, Milena Doroszko, Constanze Hantel, Sandra Sigala, Andrea Abate, Mariangela Tamburello, Katja Kiseljak‐Vassiliades, Margaret E. Wierman, Charlotte Hall, Laila Parvanta, Tarek Abdel‐Aziz, Teng‐Teng Chung, Aimee Di Marco, Fausto Palazzo, Celso E. Gómez-Sánchez, David R. Taylor, Oliver Rayner, Cristina L. Ronchi, Carles Gaston‐Massuet, Silviu Sbiera, William M Drake, Emanuel Rognoni, Matthias Kroiß, David T. Breault, Martin Faßnacht, Leonardo Guasti · 发表于：癌症：英文版 · 年份：2025 · DOI：10.1002/cac2.70012 · 被引用次数：7 · 研究领域：Adrenal and Paraganglionic Tumors、Cancer, Hypoxia, and Metabolism、Glioma Diagnosis and Treatment

Adrenocortical carcinoma (ACC) is a rare malignancy with no widely available biomarkers and commonly presents at later stages with a bleak prognosis [1]. Dysregulation of signaling pathways involved in the organogenesis and homeostasis of the adrenal cortex is implicated in its pathogenesis [2]. The paternally expressed, cleavable protein delta-like non-canonical Notch ligand 1 (DLK1) is expressed in rat adrenocortical progenitor cells [3] and in clusters of relatively undifferentiated cells in the human adrenal gland [4]. Its expression is rare in most adult human tissues but has been reported across various cancers, often associated with worse survival [5]. Here we define the role of DLK1 in adrenocortical development, self-renewal, and the development and progression of ACC. Dlk1+ cells were present in both the capsule and cortex during embryonic development but became restricted to the capsule postnatally in both male and female mice (Supplementary Figure S1), with minimal overlap in expression with Axin-2 (Wnt-active) cells, their early descendants, and platelet-derived growth factor receptor alpha (PDGFRα), a marker of mesenchymal stem/fibroblastic cells (Supplementary Figure S2). Dlk1 cells were rarely positive for Ki-67, whereas Gli1 expression in the capsule, unlike Dlk1, remained high during development and throughout postnatal life (Supplementary Figure S3). Genetic lineage tracing using inducible Dlk1CreERT2/+; RosatdTomato/+ mice showed that Dlk1+ cells functione...