A novel human tumoroid 3D model of sustained ACTH-secreting cell cultures to study critically needed therapies for Cushing's disease

Abstract

The pituitary gland is a master endocrine organ composed of distinct hormone-producing cell types that serve as sensors to integrate central and peripheral signals in order to fine-tune whole-body homeostasis and control multiple physiological functions including growth, reproduction, metabolism, and stress [1]. Classically, pituitary tumours have been considered rare and benign; however, they represent the most common intracranial neoplasms and are often aggressive. Moreover, these tumours are highly heterogeneous, displaying strikingly diverse clinical behaviours that parallel the different pituitary cell subtypes from which they arise [2]. Currently, the in vitro and in vivo pituitary tumour models available are highly limited and, in the case of the corticotroph tumours producing adrenocorticotropic hormone (ACTH), have been mainly restricted to ACTH-secreting murine cell lines (i.e., AtT-20 and AtT-20/D16v-F2) and transgenic/PDX mouse models (e.g., Crh^120/+ and POMC-SV40, among others), respectively [3].