Exploring stem cell biology in pituitary tumors and derived organoids

in Endocrine-Related Cancer
Authors:
Charlotte Nys Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), Leuven, Belgium

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https://orcid.org/0000-0001-8917-7934
,
Yu-Lun Lee Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), Leuven, Belgium

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Heleen Roose Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), Leuven, Belgium

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Freya Mertens Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), Leuven, Belgium
Department of Imaging and Pathology, UZ Leuven (University Hospitals Leuven), Leuven, Belgium

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Ellen De Pauw Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), Leuven, Belgium

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Hiroto Kobayashi Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), Leuven, Belgium
Department of Anatomy and Structural Science, Yamagata University Faculty of Medicine, Yamagata, Japan

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Raf Sciot Department of Imaging and Pathology, UZ Leuven (University Hospitals Leuven), Leuven, Belgium

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Marie Bex Department of Endocrinology, UZ Leuven (University Hospitals Leuven), Leuven, Belgium

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Georges Versyck Department of Neurosurgery, UZ Leuven (University Hospitals Leuven), Leuven, Belgium

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Steven De Vleeschouwer Department of Neurosurgery, UZ Leuven (University Hospitals Leuven), Leuven, Belgium

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Johannes Van Loon Department of Neurosurgery, UZ Leuven (University Hospitals Leuven), Leuven, Belgium

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Emma Laporte Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), Leuven, Belgium

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Hugo Vankelecom Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), Leuven, Belgium

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Correspondence should be addressed to H Vankelecom: hugo.vankelecom@kuleuven.be

*(Y-L Lee and H Roose contributed equally)

DOI:
https://doi.org/10.1530/ERC-21-0374
Volume/Issue:
Volume 29: Issue 7
Article Type:
Research Article
Page Range:
427–450
Online Publication Date:
17 Jun 2022
Copyright:
© Society for Endocrinology 2022
Restricted access
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Pituitary tumorigenesis is highly prevalent and causes major endocrine disorders. Hardly anything is known on the behavior of the local stem cells in this pathology. Here, we explored the stem cells’ biology in mouse and human pituitary tumors using transcriptomic, immunophenotyping and organoid approaches. In the prolactinoma-growing pituitary of dopamine receptor D2 knock-out mice, the stem cell population displays an activated state in terms of proliferative activity and distinct cytokine/chemokine phenotype. Organoids derived from the tumorous glands’ stem cells recapitulated these aspects of the stem cells’ activation nature. Upregulated cytokines, in particular interleukin-6, stimulated the stem cell-derived organoid development and growth process. In human pituitary tumors, cells typified by expression of stemness markers, in particular SOX2 and SOX9, were found present in a wide variety of clinical tumor types, also showing a pronounced proliferative status. Organoids efficiently developed from human tumor samples, displaying a stemness phenotype as well as tumor-specific expression fingerprints. Transcriptomic analysis revealed fading of cytokine pathways at organoid development and passaging, but their reactivation did not prove capable of rescuing early organoid expansion and passageability arrest. Taken together, our study revealed and underscored an activated phenotype of the pituitary-resident stem cells in tumorigenic glands and tumors. Our findings pave the way to defining the functional position of the local stem cells in pituitary tumor pathogenesis, at present barely known. Deeper insight can lead to more efficient and targeted clinical management, currently still not satisfactorily.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© Society for Endocrinology 2022
Page(s):
24
Received Date:
17 Mar 2022
Accepted Date:
22 Apr 2022
Print Publication Date:
01 Jul 2022
Online Publication Date:
17 Jun 2022
Keywords:
pituitary stem cells; pituitary tumors; cytokines; organoids

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