Abstract
The most common type of pituitary neoplasms is benign pituitary adenoma (PA). Clinically significant PAs affect around 0.1% of the population. Currently, there is no established human PA cell culture available and when PA tumor cells are cultured they form two distinct types depending on culturing conditions either free-floating aggregates also known as pituispheres or cells adhering to the surface of cell plates and displaying mesenchymal stem-like properties. The aim of this study was to trace the origin of sphere-forming and adherent pituitary cell cultures and characterize the potential use of these surgery derived cell lines as PA model. We carried out a paired-end exome sequencing of patients' tumor and germline DNA using Illumina NextSeq followed by characterization of corresponding PA cell cultures. Variation analysis revealed a low amount of somatic mutations (mean = 5.2, range 3–7) in exomes of PAs. Somatic mutations of the primary surgery material can be detected in the exomes of respective pituispheres, but not in exomes of respective mesenchymal stem-like cells. For the first time, we show that the genome of pituispheres represents genome of PA while mesenchymal stem cells derived from the PA tissue do not contain mutations characteristic to PA in their genome, therefore, most likely representing normal cells of pituitary or surrounding tissues. This finding indicates that pituispheres can be used as a human model of PA cells, but combination of cell culturing techniques and NGS needs to be employed to adjust for disability to propagate spheres in culturing conditions.
Highlights
The pituitary gland is an important controller of the endocrine system regulating a range of physiological processes such as metabolism, reproduction, stress responses, growth, and others via secretion of specific hormones [1]
Another type of presumably cancer stem cells (CSC) population has been isolated from pituitary adenoma (PA) tissue using adherent cell culturing method that has led to the isolation of population of mesenchymal stem-like cells (MSC). These cells fulfilled the criteria of multipotent mesenchymal stem cells described in [19], [1] were adherent in standard culture conditions, [2] expressed CD73, CD90, CD105, [3] were able to differentiate into osteoblasts, adipocytes, chondroblasts. These mesenchymal stem-like cells had limited self-renewal potential and were not able to differentiate in hormone-producing cells [20, 21]
We evaluated expression of MSC cell surface marker CD90 in both pituispheres and MSC cultures, none of the pituispheres expressed CD90, while it was highly presented in MSC cultures (Figure 3)
Summary
The pituitary gland is an important controller of the endocrine system regulating a range of physiological processes such as metabolism, reproduction, stress responses, growth, and others via secretion of specific hormones [1]. Significant pituitary adenoma (PA) is a rare non-metastasizing endocrine tumor affecting ∼1 person out of 1,000–1,300 in general population [3, 4]. Tracing Origin of Pituisphere Cells of PA are non-functioning (NFPA), not secreting any hormones in noticeable amount and their impact on patient’s health is due to the mass effect (especially affecting chiasma optica, dura mater, and portal arteries). PAs are treated via surgical resection or with drugs targeting dopamine and somatostatin receptors in prolactinsecreting and growth hormone-secreting adenomas, respectively [7, 8]
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