Endocrine Abstracts

Rationale: Pituitary tumours (PiTs) are a common and heterogeneous group of benign, slow-growing intracranial neoplasms arising from the sellar region. While recent advances have improved our knowledge of their cellular composition and the contribution of their tumour microenvironment (TME), most of PiT subtypes lack effective therapeutic treatments. Moreover, the mechanisms that occur in the early stage of PiT initiation remain to be elucidated partly due to the limited number of identified driver-mutations.

Objectives: Here, we aim to i) evaluate the consequences of pituitary tumorigenesis initiation on the remodelling of the native anterior pituitary microenvironment and ii) further model the dynamics of the functional interaction that exists between pituitary tumour cells and their microenvironment.

Approaches: We employed two main strategies based on: (1) the characterisation of the TME in spontaneous pituitary lesions found in aged mice and, (2) the development of an orthotopic mouse-model in which pituitary tumour cells were injected in the anterior pituitary gland.

Results: We confirmed that spontaneous lesions can be found in the anterior pituitary gland of aged mice. At the age of 20 months, we observed that 61.5 % of C57bl/6 mice (n=8/13) developed histological abnormalities. While only one tumour could be found, all other lesions were characterized by the presence of a moderate cell hyperplasia in areas with haemorrhages associated with the presence of siderophages. All lesions showed matrix remodelling, as demonstrated by their reduced reticular fibre network. The spatial distribution of endocrine cells was also impacted compared to control animals. Additionally, we developed a novel preclinical model based on the orthotopic injection of tumour cells in the anterior pituitary. Using this setup, we evaluated the growth of injected tumour-cells through MRI to define early and late stages of tumour progression. This preclinical model was validated with gonadotroph (αT3, LβT2), corticotroph (AtT-20) and lacto-somatotroph (GH3) rodent cells. Then, we addressed the state of the anterior pituitary environment and evaluate the presence of endothelial and myeloid cells, as well as the network of reticulin fibres in early and advanced grafted-tumours.

Conclusion: Taken together, our results support that the native environment of the anterior pituitary is subjected to a remodelling during the onset of spontaneous PiTs. Also, preliminary observations using our orthotopic approach confirmed the usefulness of this preclinical model for studying the cellular interactions between the PiT cells and their TME.