The Stem Cell Connection of Pituitary Tumors

Vankelecom, Hugo; Roose, Heleen

doi:10.3389/fendo.2017.00339

Cited by 18 publications

(27 citation statements)

References 78 publications

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“…A detailed characterization of CSC-like subpopulations was performed in the adamantinomatous craniopharyngioma, a low-grade pediatric pituitary tumor originating from Rathke's pouch, which may display an aggressive clinical course (64). Moreover, the CSC hierarchical tumorigenesis model was also proposed to be at the basis of the development of other benign tumors, and, in particular, pituitary adenomas (PAs) (54,65,66). As performed in other tumors, identification and isolation of PA stem cells (PASCs) relies on immunostaining followed by FACS or image microscopy (immunohistochemistry or immunofluorescence) in order to detect surface stem markers in post-surgical pathology preparations or, more recently, in in vitro cell cultures enriched in stem-like subpopulations by flow cytometry or growth in stem cell permissive media.…”

Section: Cancer Stem Cells In Pituitary Adenomamentioning

confidence: 99%

“…In line with these premises, PASCs, isolated as SP, showed 1.5-fold up-regulation of the multidrug transporters ABCB1 and ABCG2 (73), thus suggesting their ability to extrude cytotoxic drugs. Accordingly, Xu et al reported that PASCs from a GHoma were insensitive to both carboplatin and etoposide (69) and temozolomide resistance was described in another study (66). Interestingly, in a drug repositioning study, in vitro and in vivo treatment with disulfiram, a clinically approved drug for the treatment of alcoholism, sensitizes CD133 + /nestin + PASCs to temozolomide cytotoxicity, preventing drug-induced DNA damage repair by inhibiting O-6-methylguanine-DNA methyltransferase expression (83).…”

Section: Drug Sensitivity Of Pituitary Adenoma Stem Cellsmentioning

confidence: 99%

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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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Section: Cancer Stem Cells In Pituitary Adenomamentioning

confidence: 99%

Section: Drug Sensitivity Of Pituitary Adenoma Stem Cellsmentioning

confidence: 99%

Experimental Evidence and Clinical Implications of Pituitary Adenoma Stem Cells

et al. 2020

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“…In the last decade, experimental evidence has accumulated demonstrating that it is possible to isolate cells from human pituitary tumors that fulfill some or all the features typical of CSCs, namely, clonogenic ability in vitro , expression of stem cell markers, ability to grow as rounded cell spheres, multipotency, resistance to chemotherapeutic agents, high efflux capacity, and propagation of tumor tissue following xenotransplantation (Tables 1, 2). Since pituitary tumors are mostly benign, these cells are more correctly referred to as ‘tumor stem cells' (TSCs) (44).…”

Section: Tumor Stem Cells (Tscs) In Pituitary Tumorsmentioning

confidence: 99%

“…In another pituitary tumor type, adamantinomatous craniopharyngioma (ACP), strong evidence supports a paracrine role of TSCs in tumor development and growth by stimulation of the proliferation of adjacent cells. Genetic linage tracing experiments in a mouse model of ACP showed that SOX2 + cells targeted with mutant β-catenin did not autonomously give rise to the tumor mass but instead generated the tumor from neighboring cells in a paracrine manner (44, 56, 57).…”

Section: Tumor Stem Cells (Tscs) In Pituitary Tumorsmentioning

confidence: 99%

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

et al. 2019

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Although generally benign, pituitary tumors frequently show local invasiveness and resistance to pharmacological therapy. After the demonstration of the existence of pituitary gland stem cells, over the past decade, the presence of a stem cell subpopulation in pituitary tumors has been investigated, analogous to the cancer stem cell model developed for malignant tumors. This review recapitulates the experimental evidence supporting the existence of a population of stem-like cells in pituitary tumors, focusing on their potential role in tumor initiation, progression, recurrence and resistance to pharmacological therapy.

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“…The presence of stem cells in the pituitary gland contributes to both pituitary organ regeneration also flexible differentiation to specific hormone-secreting cells in response to the body requirement [ 8 ]. Recent evidences are in favor of connecting pituitary stem cells to the process of pituitary tumor cell formation, growth, and development [ 20 ]. Given the potential role of SOX9 in tissue regeneration as well as its relevance to the intracellular pathways regulating tumor cell growth, this study is aimed to evaluate the status of SOX9 in tumor tissues of GH- secreting pituitary adenomas at both gene and protein level to provide pieces of evidence regarding the relevance of this effector with pituitary tumors.…”

Section: Introductionmentioning

confidence: 99%

Up-regulation of sex-determining region Y-box 9 (SOX9) in growth hormone-secreting pituitary adenomas

et al. 2021

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Background Pituitary adenomas are benign brain tumors that cause considerable morbidity and neurological symptoms. SOX9 as a regulatory transcriptional mediator affects normal and tumor cell growth with an undefined role in pituitary adenomas pathogenesis. Thus, in the present study, the expression pattern of SOX9 in GH-secreting pituitary tumors and normal pituitary tissues is investigated. Methods The SOX9 gene expression level was evaluated in 60 pituitary tissues including different types of GH-secreting adenomas and normal pituitary tissues through Real-Time PCR. The protein level of SOX9 was assessed using immunohistochemistry. The correlations of SOX9 gene and protein expression level with the patient’s clinical and pathological features were considered. Results The SOX9 over-expression was detected in GH-secreting adenomas tumor tissues compared to normal pituitary tissues which were accompanied by overexpression of SOX9 protein in tumor tissues. The over-expression of SOX9 had a significant impact on GH-secreting adenomas tumor incidence with the odds ratio of 8.4 and the diagnostic value of SOX9 was considerable. The higher level of SOX9 expression was associated with invasive and macro tumors in GH-secreting pituitary adenoma patients. The positive correlation of SOX9 gene and protein level was observed and the tumor size and tumor invasive features were valuable in predicting SOX9 expression level in GH-producing pituitary tumors. Conclusion The study provided the first shreds of evidence regarding the expression pattern of SOX9 in the GH- secreting pituitary adenomas at both gene and protein levels which may emphasize the possible involvement of SOX9 as a mediator in pituitary adenoma tumor formation also open up new intrinsic molecular mechanism regarding pituitary adenoma pathogenesis.

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The Stem Cell Connection of Pituitary Tumors

Cited by 18 publications

References 78 publications

Experimental Evidence and Clinical Implications of Pituitary Adenoma Stem Cells

Experimental Evidence and Clinical Implications of Pituitary Adenoma Stem Cells

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

Up-regulation of sex-determining region Y-box 9 (SOX9) in growth hormone-secreting pituitary adenomas

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