Stem Cell Transcription Factor Sox2 Is Expressed in a Subset of Folliculo-stellate Cells of Growth Hormone–Producing Pituitary Neuroendocrine Tumours and Its Expression Shows No Association with Tumour Size or IGF1 Levels: a Clinicopathological Study of 109 Cases

Soukup, Jiří; Česák, Tomáš; Hornychová, Helena; Michalová, Květoslava; Michnová, Ľudmila; Netuka, David; J, Cáp; Gabalec, Filip

doi:10.1007/s12022-020-09634-1

Cited by 6 publications

(5 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most studies targeted rodent species and revealed that Sox2 + adult stem/progenitor cells are located within two types of niches: the marginal cell layer lining the pituitary cleft, and the cell clusters scattered in the anterior lobe parenchyma (16,19,25,32). A similar organization of stem/ progenitor cell niches was also suggested in humans (11,31,33,34) and cattle (35,36) by analyzing the expression of SOX2 and other candidate markers. Moreover, a clonogenic cell population, which expresses LHX3 and which can differentiate into prolactin + cells, was isolated from normal human pituitaries from autopsies (age 51-83) (12), supporting the existence of functional stem/progenitor cells in the human pituitary gland throughout life.…”

Section: Pitx1 and Lhx3)mentioning

confidence: 86%

EpCAM Is a Surface Marker for Enriching Anterior Pituitary Cells From Human Hypothalamic-Pituitary Organoids

et al. 2022

View full text Add to dashboard Cite

Human stem cell-derived organoid culture enables the in vitro analysis of the cellular function in three-dimensional aggregates mimicking native organs, and also provides a valuable source of specific cell types in the human body. We previously established organoid models of the hypothalamic-pituitary (HP) complex using human pluripotent stem cells. Although the models are suitable for investigating developmental and functional HP interactions, we consider that isolated pituitary cells are also useful for basic and translational research on the pituitary gland, such as stem cell biology and regenerative medicine. To develop a method for the purification of pituitary cells in HP organoids, we performed surface marker profiling of organoid cells derived from human induced pluripotent stem cells (iPSCs). Screening of 332 human cell surface markers and a subsequent immunohistochemical analysis identified epithelial cell adhesion molecule (EpCAM) as a surface marker of anterior pituitary cells, as well as their ectodermal precursors. EpCAM was not expressed on hypothalamic lineages; thus, anterior pituitary cells were successfully enriched by magnetic separation of EpCAM+ cells from iPSC-derived HP organoids. The enriched pituitary population contained functional corticotrophs and their progenitors; the former responded normally to a corticotropin-releasing hormone stimulus. Our findings would extend the applicability of organoid culture as a novel source of human anterior pituitary cells, including stem/progenitor cells and their endocrine descendants.

show abstract

Section: Pitx1 and Lhx3)mentioning

confidence: 86%

EpCAM Is a Surface Marker for Enriching Anterior Pituitary Cells From Human Hypothalamic-Pituitary Organoids

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In total, 114 tumour samples from 110 patients with symptomatic acromegaly were collected in the form of formalin‐fixed paraffin‐embedded tissue. The patient cohort was identical with the cohort described in detail by the authors in previous articles 16,17 . Radiological data (size, Knosp grade of invasion), laboratory data (plasma levels of GH, prolactin, thyroid‐stimulating hormone (TSH) and levels of insulin‐like growth factor 1 (IGF1) expressed as a multiple of age‐adjusted normal levels) were collected either from the RESET registry or from the databases of the participating institutions.…”

Section: Methodsmentioning

confidence: 99%

“…These tumours showed a larger size, lower levels of GH and a greater tendency for prolactin co‐expression in one study, 12 while other studies have not discussed these in more detail. As the lack of identifiable CK pattern significantly impairs the prognostic and predictive value of the histopathological report, we decided to more clearly characterise the clinicopathological features of 10 CK 18‐negative tumours from the cohort of patients that we have described previously 16,17 …”

Section: Introductionmentioning

confidence: 99%

Cytokeratin 8/18‐negative somatotroph pituitary neuroendocrine tumours (PitNETs, adenomas) show variable morphological features and do not represent a clinicopathologically distinct entity

et al. 2021

Self Cite

View full text Add to dashboard Cite

Aims In somatotroph pituitary neuroendocrine tumours (adenomas), a pattern of cytokeratin (CK) 18 expression is used for tumour subclassification, with possible clinical implications. Rare somatotroph tumours do not express CK 18. We aimed to characterise this subset clinically and histologically. Methods and results Clinical and pathological data for the study were derived from a previously published data set of a cohort of 110 patients with acromegaly. Data included serum levels of insulin‐like growth factor 1 (IGF1), growth hormone (GH), prolactin and thyroid‐stimulating hormone (TSH), tumour diameter, tumour invasion defined by Knosp grade and immunohistochemical data concerning the expression of Ki67, p53, E‐cadherin, somatostatin receptor (SSTR)1, SSTR2A, SSTR3, SSTR5 and D2 dopamine receptor. Additional immunohistochemical analysis (AE1/3, CK 8/18, vimentin, neurofilament light chain, internexin‐α) was performed. CK 18 was negative in 10 of 110 (9.1%) tumours. One of these tumours was immunoreactive with CK 8/18 antibody, while the remainder expressed only internexin‐α intermediate filament in patterns similar to CK 18 (perinuclear fibrous bodies). CK‐negative tumours showed no significant differences with respect to biochemical, radiological or pathological features. They showed significantly higher expression of SSTR2A compared to the sparsely granulated subtype and significantly lower expression of E‐cadherin compared to the non‐sparsely granulated subtypes of tumours. The tumours showed divergent morphology and hormonal expression: two corresponded to densely granulated tumours and three showed co‐expression of prolactin and morphology of either mammosomatotroph or somatotroph–lactotroph tumours. Four tumours showed morphology and immunoprofile compatible with plurihormonal Pit1‐positive tumours. Conclusions CK‐negative somatotroph tumours do not represent a distinct subtype of somatotroph tumours, and can be further subdivided according to their morphology and immunoprofile.

show abstract

“…Insulin stimulation also enhanced ACTH production in the cultures, suggesting increased differentiation of stem cells towards the corticotroph lineage 28 . However, in clinicopathological studies, the expression of the transcription factor SRY-Box transcription factor 2 (SOX2), which is a marker of stem cells in normal pituitaries, did not correlate with IGF1 levels in hormone-producing pituitary endocrine tumors 83 .…”

Section: Metabolic Disorders and Tumorigenesis In The Hpa Axismentioning

confidence: 99%

Sensitivity of the Neuroendocrine Stress Axis in Metabolic Diseases

Cozma,

Siatra,

Bornstein

et al. 2024

Horm Metab Res

View full text Add to dashboard Cite

Metabolic diseases are prevalent in modern society and have reached pandemic proportions. Metabolic diseases have systemic effects on the body and can lead to changes in the neuroendocrine stress axis, the critical regulator of the body’s stress response. These changes may be attributed to rising insulin levels and the release of adipokines and inflammatory cytokines by adipose tissue, which affect hormone production by the neuroendocrine stress axis. Chronic stress due to inflammation may exacerbate these effects. The increased sensitivity of the neuroendocrine stress axis may be responsible for the development of metabolic syndrome, providing a possible explanation for the high prevalence of severe comorbidities such as heart disease and stroke associated with metabolic disease. In this review, we address current knowledge of the neuroendocrine stress axis in response to metabolic disease and discuss its role in developing metabolic syndrome.

show abstract

Stem Cell Transcription Factor Sox2 Is Expressed in a Subset of Folliculo-stellate Cells of Growth Hormone–Producing Pituitary Neuroendocrine Tumours and Its Expression Shows No Association with Tumour Size or IGF1 Levels: a Clinicopathological Study of 109 Cases

Cited by 6 publications

References 21 publications

EpCAM Is a Surface Marker for Enriching Anterior Pituitary Cells From Human Hypothalamic-Pituitary Organoids

EpCAM Is a Surface Marker for Enriching Anterior Pituitary Cells From Human Hypothalamic-Pituitary Organoids

Cytokeratin 8/18‐negative somatotroph pituitary neuroendocrine tumours (PitNETs, adenomas) show variable morphological features and do not represent a clinicopathologically distinct entity

Sensitivity of the Neuroendocrine Stress Axis in Metabolic Diseases

Contact Info

Product

Resources

About