Adamantinomatous craniopharyngiomas express tumor stem cell markers in cells with activated Wnt signaling: further evidence for the existence of a tumor stem cell niche?

Hölsken, Annett; Stache, Christina; Schlaffer, Sven; Flitsch, Jörg; Fahlbusch, Rudolf; Buchfelder, Michael; Buslei, Rolf

doi:10.1007/s11102-013-0543-8

Cited by 56 publications

(40 citation statements)

References 50 publications

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“…3,4,15 This, coupled with their stem cell-like markers, e.g., CD44, SOX2, have made these clusters of particular interest when studying the signaling pathways underlying the development and progression of ACP. 4,24 Indeed activation of CTNNB1 in adult pituitary SOX2-positive stem cells alone leads to tumors resembling ACP. 4 Studies have shown that these clusters may act as signaling centers expressing high levels of secreted factors such as SHH, FGFs, BMPs and WNTs, with paracrine actions on neighboring cells.…”

Section: Molecular Biology Of B-cateninaccumulating Cell Clustersmentioning

confidence: 99%

Molecular pathology of adamantinomatous craniopharyngioma: review and opportunities for practice

Apps¹,

Martinez-Barbera²

2016

FOC

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Since the first identification of CTNNB1 mutations in adamantinomatous craniopharyngioma (ACP), much has been learned about the molecular pathways and processes that are disrupted in ACP pathogenesis. To date this understanding has not translated into tangible patient benefit. The recent development of novel techniques and a range of preclinical models now provides an opportunity to begin to support treatment decisions and develop new therapeutics based on molecular pathology. In this review the authors summarize many of the key findings and pathways implicated in ACP pathogenesis and discuss the challenges that need to be tackled to translate these basic science findings for the benefit of patients.

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Section: Molecular Biology Of B-cateninaccumulating Cell Clustersmentioning

confidence: 99%

Molecular pathology of adamantinomatous craniopharyngioma: review and opportunities for practice

Apps¹,

Martinez-Barbera²

2016

FOC

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“…9,11,12,24,28,38 As a result of this mechanism, nuclear accumulation of b-catenin is a histological hallmark of CTNNB1 mutation. 10,12,16,26,41 In the case of craniopharyngiomas, mutation of CTNNB1 has been described in 69%-100% 9,20,28 of ACP specimens, while it is not routinely observed in PCP or other parasellar tumors. 9,28 In the most detailed study to date, CTNNB1 mutation was identified in 95% of ACP specimens, using massively parallel sequencing and targeted genotyping.…”

Section: Ctnnb1 Mutationmentioning

confidence: 99%

“…26 As with therapies directed at the SHH pathway, those targeting the EGF pathway require further clarification through preclinical study before they could enter clinical use and impact neurosurgical care.…”

mentioning

confidence: 99%

Potential evolution of neurosurgical treatment paradigms for craniopharyngioma based on genomic and transcriptomic characteristics

Robinson

Santagata

Hankinson

2016

FOC

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The recent genomic and transcriptomic characterization of human craniopharyngiomas has provided important insights into the pathogenesis of these tumors and supports that these tumor types are distinct entities. Critically, the insights provided by these data offer the potential for the introduction of novel therapies and surgical treatment paradigms for these tumors, which are associated with high morbidity rates and morbid conditions. Mutations in the CTNNB1 gene are primary drivers of adamantinomatous craniopharyngioma (ACP) and lead to the accumulation of β-catenin protein in a subset of the nuclei within the neoplastic epithelium of these tumors. Dysregulation of epidermal growth factor receptor (EGFR) and of sonic hedgehog (SHH) signaling in ACP suggest that paracrine oncogenic mechanisms may underlie ACP growth and implicate these signaling pathways as potential targets for therapeutic intervention using directed therapies. Recent work shows that ACP cells have primary cilia, further supporting the potential importance of SHH signaling in the pathogenesis of these tumors. While further preclinical data are needed, directed therapies could defer, or replace, the need for radiation therapy and/or allow for less aggressive surgical interventions. Furthermore, the prospect for reliable control of cystic disease without the need for surgery now exists. Studies of papillary craniopharyngioma (PCP) are more clinically advanced than those for ACP. The vast majority of PCPs harbor the BRAFv600e mutation. There are now 2 reports of patients with PCP that had dramatic therapeutic responses to targeted agents. Ongoing clinical and research studies promise to not only advance our understanding of these challenging tumors but to offer new approaches for patient management.

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“…The stem cell markers SOX2 [16] , POU1F5/OCT4 [16], SOX9 [16,17], and CD44 [18] have previously been described in association with ACP. In this study, we aimed to increase current knowledge regarding the expression patterns of pituitary stem cell markers in ACP and pituitary adenomas, including the markers DLL4, NANOG, NOTCH2, and POU1F5/OCT4, to better understand the tumour development and recurrence process.…”

Section: Introductionmentioning

confidence: 99%

Differential Expression of Stem Cell Markers in Human Adamantinomatous Craniopharyngioma and Pituitary Adenoma

Chang¹,

Araujo²,

Cirqueira³

et al. 2016

Neuroendocrinology

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Background/Aims: Although craniopharyngioma (CP) is histologically benign, it is a pituitary tumour that grows rapidly and often recurs. Adamantinomatous CP (ACP) was associated with an activating mutation in β-catenin, and it has been postulated that pituitary stem cells might play a role in oncogenesis in human ACP. Stem cells have also been identified in pituitary adenoma. Our aim was to characterize the expression pattern of ABCG2, CD44, DLL4, NANOG, NOTCH2, POU5F1/OCT4, SOX2, and SOX9 stem cell markers in human ACP and pituitary adenoma. Methods and Results: We studied 33 patients (9 ACP and 24 adenoma) using real-time quantitative PCR (RT-qPCR) and immunohistochemistry. SOX9 was up-regulated in ACP, exhibiting positive immunostaining in the epithelium and stroma, with the highest expression in patients with recurrence. CD44 was overexpressed in ACP as confirmed by immunohistochemistry. SOX2 did not significantly differ among the tumour types. The RT-qPCR array showed an increased expression of MKI67,OCT4/POU5F1, and DLL4 in all tumours. NANOG was decreased in ACP. ABCG2 was down-regulated in most of the tumours. NOTCH2 was significantly decreased in the adenomas. Conclusion: Our results confirm the presence of stem cell markers in human pituitary tumours as well as the different expression patterns of ACP and adenoma. These findings suggest that ACP may originate from a more undifferentiated cell cluster. Additionally, SOX9 immunodetection in the stroma and the highest expression levels related to the relapse of patients suggest a contribution to the aggressive behaviour and high recurrence of this tumour type.

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Adamantinomatous craniopharyngiomas express tumor stem cell markers in cells with activated Wnt signaling: further evidence for the existence of a tumor stem cell niche?

Cited by 56 publications

References 50 publications

Molecular pathology of adamantinomatous craniopharyngioma: review and opportunities for practice

Molecular pathology of adamantinomatous craniopharyngioma: review and opportunities for practice

Potential evolution of neurosurgical treatment paradigms for craniopharyngioma based on genomic and transcriptomic characteristics

Differential Expression of Stem Cell Markers in Human Adamantinomatous Craniopharyngioma and Pituitary Adenoma

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