Stem Cells in Pituitary Tumors: Experimental Evidence Supporting Their Existence and Their Role in Tumor Clinical Behavior

Mantovani, Giovanna; Giardino, Elena; Treppiedi, Donatella; Catalano, Rosa; Mangili, Federica; Spada, Anna; Arosio, Maura; Peverelli, Erika

doi:10.3389/fendo.2019.00745

Cited by 11 publications

(4 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recent advances have led to the development of pituitary tissue generated organoids, but these are limited to the use of transgenic mouse models as the source 20,21,34 . In addition, there are the reports of mouse nonadherent spheres with stem/progenitor characteristics 35 , and human embryonic stem cell generated spheroids or patient derived tumoroids that also lack a multicellular identify and consist of poorly differentiated cells 22,[36][37][38][39][40] .…”

Section: Discussionmentioning

confidence: 99%

Development of Human Pituitary Adenoma Organoids to Facilitate Effective Targeted Treatments of Cushing's Disease.

Zavros

Chakrabarti

Pandey

et al. 2022

Preprint

View full text Add to dashboard Cite

Cushing's disease (CD) is a serious endocrine disorder caused by dysregulated adrenocorticotropic hormone (ACTH)-secreting pituitary tumor that stimulates the adrenal glands to overproduce cortisol. Chronic exposure to excess cortisol has detrimental effects on health, including increased stroke rates, diabetes, obesity, cognitive impairment, anxiety, depression, and death. The first-line treatment for CD is pituitary surgery, which is followed by disease remission. Current surgical remission rates reported range from 47–85% depending on several remission criteria. The lack of specificity, poor tolerability, and low efficacy of the subsequent second-line medical therapies makes CD a medical therapeutic challenge. One major limitation that hinders the development of specific medical therapies is the lack of human relevant model systems that recapitulate the cellular composition of pituitary adenomas. Human pituitary adenoma tissue was harvested during transsphenoidal surgery from CD patients to generate organoids (hPITOs). hPITOs generated from corticotroph, lactotroph, gonadotroph and somatotroph adenomas exhibited morphological diversity among the organoid lines between individual patients and amongst subtypes. The similarity in cell lineages between the organoid line and the patient’s tumor was validated by comparing the neuropathology report to the expression pattern of pituitary adenoma specific markers using spectral flow cytometry and exome sequencing. A high-throughput drug screen demonstrated patient-specific drug responses of hPITOs amongst each adenoma subtype. Generation of induced pluripotent stem cells (iPSCs) from patients carrying germline mutations relevant to CD exhibited dysregulated cell lineage commitment. The human pituitary adenoma organoids represent a novel approach in how we model complex pathologies in CD patients that may enable more effective personalized medicine for these patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Development of Human Pituitary Adenoma Organoids to Facilitate Effective Targeted Treatments of Cushing's Disease.

Zavros

Chakrabarti

Pandey

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Although S-100β, SOX2, SOX9 [18,19], PITX1, GFRa2, SCA1, Nestin and PROP-1 [20] have been used as markers of PGSCs, no highly specific markers exist for PGSCs because PGSCs have been isolated using different markers in each study [21].…”

Section: Markersmentioning

confidence: 99%

Recent Progress in Stem Cell Research of the Pituitary Gland and Pituitary Adenoma

2020

View full text Add to dashboard Cite

Regenerative medicine and anti-tumoral therapy have been developed through understanding tissue stem cells and cancer stem cells (CSCs). The concept of tissue stem cells has been applied to the pituitary gland (PG). Recently, PG stem cells (PGSCs) were successfully differentiated from human embryonic stem cells and induced pluripotent stem cells, showing an in vivo therapeutic effect in a hypopituitary model. Pituitary adenomas (PAs) are common intracranial neoplasms that are generally benign, but treatment resistance remains a major concern. The concept of CSCs applies to PA stem cells (PASCs). Genetic alterations in human PGSCs result in PASC development, leading to treatment-resistant PAs. To determine an efficient treatment against refractory PAs, it is of paramount importance to understand the relationship between PGSCs, PASCs and PAs. The goal of this review is to discuss several new findings about PGSCs and the roles of PASCs in PA tumorigenesis.

show abstract

“…[24][25][26][27][28] These CSC are similar to normal tissue SC because they retain the capability to self-renew and give rise to cancer cell progenitors with a multipotent differentiation potential. 12 The existence of CSC in pituitary adenomas has been recently begun to be reported and, because most pituitary tumors are benign, the CSC should be more correctly referred to being tumor stem cells (TSC) 29,30 or pituitary adenoma stem cells. 31 The first evidence of the presence of TSC was reported in pituitary adenomas with CD133 and Nestin positive cells.…”

Section: Introductionmentioning

confidence: 99%

Changes of stem cell niche during experimental pituitary tumor development

Guido

Sosa

Pérez

et al. 2021

J Neuroendocrinology

View full text Add to dashboard Cite

To investigate the putative stem cell/tumor stem cell (SC/TSC) niche contribution to hyperplasic/adenomatous pituitary lesions, we analyzed variation in the pituitary stem cell population during the development of experimental pituitary tumors. Pituitary tumors were induced in female F344 rats with estradiol benzoate for 5, 10, 20 and 30 days. Cells positive for GFRa2, Sox2, Sox9, Nestin, CD133 and CD44 were identified in the marginal zone and in the adenoparenchyma in both control and 30D groups, with predominant adenoparenchyma localization of GRFa2 and SOX9 found in tumoral pituitaries. GFRa2, Nestin, CD133 and CD44 were upregulated at the initial stages of tumor growth, whereas Sox9 significantly decreased at 5D, with Sox2 remaining invariable during the hyperplasic/adenomatous development. In addition, isolated pituispheres from normal and tumoral pituitary glands enriched in SC/TSC were characterized. Pituispheres from the 30D glands were positive for the above-mentioned markers and showed a significant increase in the proliferation. In conclusion, our data revealed pituitary SC pool fluctuations during hyperplastic/adenomatous development, with differential localization of the SC/TSC niche in this process. These findings may help to provide a better understanding of these cell populations, which is crucial for achieving advancements in the field of pituitary tumor biology.

show abstract

Stem Cells in Pituitary Tumors: Experimental Evidence Supporting Their Existence and Their Role in Tumor Clinical Behavior

Cited by 11 publications

References 58 publications

Development of Human Pituitary Adenoma Organoids to Facilitate Effective Targeted Treatments of Cushing's Disease.

Development of Human Pituitary Adenoma Organoids to Facilitate Effective Targeted Treatments of Cushing's Disease.

Recent Progress in Stem Cell Research of the Pituitary Gland and Pituitary Adenoma

Changes of stem cell niche during experimental pituitary tumor development

Contact Info

Product

Resources

About