Pituitary Stem Cells: Quest for Hidden Functions

Vankelecom, Hugo

doi:10.1007/978-3-319-41603-8_7

Cited by 11 publications

(12 citation statements)

References 107 publications

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“…Because pituitary tumors are generally not considered as cancer, we will further not use the term CSC but designate this tumor-driving population as “tumor stem cells” (TSC). Extensive reviews have been published on this topic before ( 19 – 24 ). Here, we will briefly summarize and discuss the more recent findings.…”

Section: Tumor Stem Cell Candidatesmentioning

confidence: 99%

The Stem Cell Connection of Pituitary Tumors

Vankelecom

Roose

2017

Front. Endocrinol.

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Tumors in the pituitary gland are typically benign but cause serious morbidity due to compression of neighboring structures and hormonal disruptions. Overall, therapy efficiency remains suboptimal with negative impact on health and comfort of life, including considerable risk of therapy resistance and tumor recurrence. To date, little is known on the pathogenesis of pituitary tumors. Stem cells may represent important forces in this process. The pituitary tumors may contain a driving tumor stem cell population while the resident tissue stem cells may be directly or indirectly linked to tumor development and growth. Here, we will briefly summarize recent studies that afforded a glance behind the scenes of this stem cell connection. A better knowledge of the mechanisms underlying pituitary tumorigenesis is essential to identify more efficacious treatment modalities and improve clinical management.

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Section: Tumor Stem Cell Candidatesmentioning

confidence: 99%

The Stem Cell Connection of Pituitary Tumors

Vankelecom

Roose

2017

Front. Endocrinol.

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“…The marginal zone and parenchymal clusters are proposed to represent plural stem cell niches in the pituitary to enable swift adaptation during (subtle) cell remodeling processes (Vankelecom 2012, Vankelecom & Chen 2014. The different niches appear physically interconnected in a 3D network , Mollard et al 2012, Vankelecom & Chen 2014, Vankelecom 2016. However, whether the stem cells at the different locations exhibit different properties, regulation and function is not clear.…”

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confidence: 99%

Pituitary stem cell regulation: who is pulling the strings?

Cox

Roose

Vennekens

et al. 2017

Journal of Endocrinology

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The pituitary gland plays a pivotal role in the endocrine system, steering fundamental processes of growth, metabolism, reproduction and coping with stress. The adult pituitary contains resident stem cells, which are highly quiescent in homeostatic conditions. However, the cells show marked signs of activation during processes of increased cell remodeling in the gland, including maturation at neonatal age, adaptation to physiological demands, regeneration upon injury and growth of local tumors. Although functions of pituitary stem cells are slowly but gradually uncovered, their regulation largely remains virgin territory. Since postnatal stem cells in general reiterate embryonic developmental pathways, attention is first being given to regulatory networks involved in pituitary embryogenesis. Here, we give an overview of the current knowledge on the NOTCH, WNT, epithelial-mesenchymal transition, SHH and Hippo pathways in the pituitary stem/progenitor cell compartment during various (activation) conditions from embryonic over neonatal to adult age. Most information comes from expression analyses of molecular components belonging to these networks, whereas functional extrapolation is still very limited. From this overview, it emerges that the 'big five' embryonic pathways are indeed reiterated in the stem cells of the 'lazy' homeostatic postnatal pituitary, further magnified en route to activation in more energetic, physiological and pathological remodeling conditions. Increasing the knowledge on the molecular players that pull the regulatory strings of the pituitary stem cells will not only provide further fundamental insight in postnatal pituitary homeostasis and activation, but also clues toward the development of regenerative ideas for improving treatment of pituitary deficiency and tumors.

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“…As observed for stem cells from different tissue, Sox2 + /Sox9 + /E-cadherin + PSCs have been detected within specific niches, which in adult mouse and rat anterior pituitary were identified in the marginal zone (21,29,32,39,41), and within the anterior lobe parenchyma (21,25,(42)(43)(44). A similar organization and expression profile of PSCs has been described in the human gland (27,32), although their regulation, likely involving soluble factors, cell surface proteins and extracellular matrices, is still not completely clear (31,42,(44)(45)(46)(47).…”

Section: Pituitary Stem Cells In Cell Turnover and Responses To Hormonesmentioning

confidence: 79%

Experimental Evidence and Clinical Implications of Pituitary Adenoma Stem Cells

et al. 2020

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Pituitary adenomas, accounting for 15% of diagnosed intracranial neoplasms, are usually benign and pharmacologically and surgically treatable; however, the critical location, mass effects and hormone hypersecretion sustain their significant morbidity. Approximately 35% of pituitary tumors show a less benign course since they are highly proliferative and invasive, poorly resectable, and likely recurring. The latest WHO classification of pituitary tumors includes pituitary transcription factor assessment to determine adenohypophysis cell lineages and accurate designation of adenomas, nevertheless little is known about molecular and cellular pathways which contribute to pituitary tumorigenesis. In malignant tumors the identification of cancer stem cells radically changed the concepts of both tumorigenesis and pharmacological approaches. Cancer stem cells are defined as a subset of undifferentiated transformed cells from which the bulk of cancer cells populating a tumor mass is generated. These cells are able to self-renew, promoting tumor progression and recurrence of malignant tumors, also conferring cytotoxic drug resistance. On the other hand, the existence of stem cells within benign tumors is still debated. The presence of adult stem cells in human and murine pituitaries where they sustain the high plasticity of hormone-producing cells, allowed the hypothesis that putative tumor stem cells might exist in pituitary adenomas, reinforcing the concept that the cancer stem cell model could also be applied to pituitary tumorigenesis. In the last few years, the isolation and phenotypic characterization of putative pituitary adenoma stem-like cells was performed using a wide and heterogeneous variety of experimental models and techniques, although the role of these cells in adenoma initiation and progression is still not completely definite. The assessment of possible pituitary adenoma-initiating cell population would be of extreme relevance to better understand pituitary tumor biology and to identify novel potential diagnostic markers and pharmacological targets. In this review, we summarize the most updated studies focused on the definition of pituitary adenoma stem cell phenotype and functional features, highlighting the biological processes and intracellular pathways potentially involved in driving tumor growth, relapse, and therapy resistance.

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Pituitary Stem Cells: Quest for Hidden Functions

Cited by 11 publications

References 107 publications

The Stem Cell Connection of Pituitary Tumors

The Stem Cell Connection of Pituitary Tumors

Pituitary stem cell regulation: who is pulling the strings?

Experimental Evidence and Clinical Implications of Pituitary Adenoma Stem Cells

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