2026/04/22 by Yasmine Kemkem, Mark Quinn, Bence Kövér +20 · 2 voices · 1 citation
Medicine · Biochemistry, Genetics and Molecular Biology · #Adrenal and Paraganglionic Tumors #Cancer, Hypoxia, and Metabolism #Pituitary Gland Disorders and Treatments
paper · doi:10.1530/erc-25-0242
openalex created_date 2025/10/10 · openalex publication_date 2026/04/22 · openalex updated_date 2026/07/28
Phaeochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumours that arise in the neural crest (NC)-derived adrenal medulla and the paraganglia, respectively. Approximately 10-15% of patients with PCCs and 35-40% with PGLs go on to develop metastatic disease, leading to a reported median overall survival of 7 years. The development of prognostic markers and subsequent personal therapeutic strategies are hindered by a lack of understanding of tumourigenesis. In other organs, cells with stem-like properties are at the root of tumour initiation and maintenance, due to their ability to self-renew and give rise to differentiated cells. We have recently shown that, in the human adrenal, a subset of sustentacular cells, endowed with a support role, are in fact SOX2+ postnatal adrenomedullary stem cells that are specified along the NC migratory route. In this study, we intended to determine if SOX2+ cells in PCCs and PGLs can behave as tumour-initiating stem cells. Using expression and transcriptomic studies, we demonstrate the presence of SOX2/SOX2-expressing cells across a broad range of PCCs and PGLs, irrespective of tumour aggressiveness, location, and causative mutation. In silico analyses reveal the co-expression of SOX2 and chromaffin cell markers in the tumour and reveal the active proliferation of these double-positive cells. Isolation of these cells in vitro in stem cell-promoting media, and their xenotransplantation on chicken chorioallantoic membranes, demonstrates that they have the potential to expand and metastasise in ovo, supporting their potential as tumour-initiating cells.