Pituitary tumors contain a side population with tumor stem cell-associated characteristics

Autores
Mertens, Freya; Gremeaux, Lies; Chen, Jianghai; Fu, Qiuli; Willems, Christophe; Roose, Heleen; Govaere, Olivier; Roskams, Tania; Cristina, Silvia Carolina; Becu Villalobos, Damasia; Joriseen, Mark; Vander Poorten, Vincent; Bex, Marie; Van Loon, Johannes; Vankelecom, Hugo
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Pituitary adenomas cause significant endocrine and mass-related morbidity. Little is known about the mechanisms that underlie pituitary tumor pathogenesis. In the present study, we searched for a side population (SP) in pituitary tumors representing cells with high efflux capacity and potentially enriched for tumor stem cells (TSCs). Human pituitary adenomas contain a SP irrespective of hormonal phenotype. This adenoma SP, as well as the purified SP (pSP) that is depleted from endothelial and immune cells, is enriched for cells that express ‘tumor stemness’ markers and signaling pathways, including epithelial–mesenchymal transition (EMT)-linked factors. Pituitary adenomas were found to contain self-renewing sphere-forming cells, considered to be a property of TSCs. These sphere-initiating cells were recovered in the pSP. Because benign pituitary adenomas do not grow in vitro and have failed to expand in immunodeficient mice, the pituitary tumor cell line AtT20 was further used. We identified a SP in this cell line and found it to be more tumorigenic than the non-SP ‘main population’. Of the two EMT regulatory pathways tested, the inhibition of chemokine (C-X-C motif) receptor 4 (CXCR4) signaling reduced EMT-associated cell motility in vitro as well as xenograft tumor growth, whereas the activation of TGFβ had no effect. The human adenoma pSP also showed upregulated expression of the pituitary stem cell marker SOX2. Pituitaries from dopamine receptor D2 knockout (Drd2−/−) mice that bear prolactinomas contain more pSP, Sox2+, and colony-forming cells than WT glands. In conclusion, we detected a SP in pituitary tumors and identified TSC-associated characteristics. The present study adds new elements to the unraveling of pituitary tumor pathogenesis and may lead to the identification of new therapeutic targets.
Fil: Mertens, Freya. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica
Fil: Gremeaux, Lies. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica; Bélgica
Fil: Chen, Jianghai. Huazhong University of Science and Technology. Tongji Medical College Union Hospital; China. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica
Fil: Fu, Qiuli. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica. Zhejiang Provincial Key Laboratory of Ophthalmology; China. Medical College of Zhejiang University. Eye Center of the 2nd Affiliated Hospital; China
Fil: Willems, Christophe. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica
Fil: Roose, Heleen. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica
Fil: Govaere, Olivier. KU Leuven. Department of Imaging and Pathology; Bélgica
Fil: Roskams, Tania. KU Leuven. Department of Imaging and Pathology; Bélgica
Fil: Cristina, Silvia Carolina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina
Fil: Becu Villalobos, Damasia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Joriseen, Mark. University Hospitals Leuven. Unit Head and Neck Oncology; Bélgica
Fil: Vander Poorten, Vincent. University Hospitals Leuven. Research Group Experimental Oto-Rhino-Laryngology, ; Bélgica
Fil: Bex, Marie. University Hospitals Leuven. Unit Clinical and Experimental Endocrinology; Bélgica
Fil: Van Loon, Johannes. University Hospitals Leuven. Research Group Experimental Neurosurgery and Neuroanatomy; Bélgica
Fil: Vankelecom, Hugo. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica
Materia
PITUITARY
STEM CELLS
ADENOMA
MICROARRAY
CANCER STEM CELL
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/5539
Acceder
id CONICETDig_3a709df3cbf59e926857b121646e48a6
oai_identifier_str oai:ri.conicet.gov.ar:11336/5539
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Pituitary tumors contain a side population with tumor stem cell-associated characteristicsMertens, FreyaGremeaux, LiesChen, JianghaiFu, QiuliWillems, ChristopheRoose, HeleenGovaere, OlivierRoskams, TaniaCristina, Silvia CarolinaBecu Villalobos, DamasiaJoriseen, MarkVander Poorten, VincentBex, MarieVan Loon, JohannesVankelecom, HugoPITUITARYSTEM CELLSADENOMAMICROARRAYCANCER STEM CELLhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Pituitary adenomas cause significant endocrine and mass-related morbidity. Little is known about the mechanisms that underlie pituitary tumor pathogenesis. In the present study, we searched for a side population (SP) in pituitary tumors representing cells with high efflux capacity and potentially enriched for tumor stem cells (TSCs). Human pituitary adenomas contain a SP irrespective of hormonal phenotype. This adenoma SP, as well as the purified SP (pSP) that is depleted from endothelial and immune cells, is enriched for cells that express ‘tumor stemness’ markers and signaling pathways, including epithelial–mesenchymal transition (EMT)-linked factors. Pituitary adenomas were found to contain self-renewing sphere-forming cells, considered to be a property of TSCs. These sphere-initiating cells were recovered in the pSP. Because benign pituitary adenomas do not grow in vitro and have failed to expand in immunodeficient mice, the pituitary tumor cell line AtT20 was further used. We identified a SP in this cell line and found it to be more tumorigenic than the non-SP ‘main population’. Of the two EMT regulatory pathways tested, the inhibition of chemokine (C-X-C motif) receptor 4 (CXCR4) signaling reduced EMT-associated cell motility in vitro as well as xenograft tumor growth, whereas the activation of TGFβ had no effect. The human adenoma pSP also showed upregulated expression of the pituitary stem cell marker SOX2. Pituitaries from dopamine receptor D2 knockout (Drd2−/−) mice that bear prolactinomas contain more pSP, Sox2+, and colony-forming cells than WT glands. In conclusion, we detected a SP in pituitary tumors and identified TSC-associated characteristics. The present study adds new elements to the unraveling of pituitary tumor pathogenesis and may lead to the identification of new therapeutic targets.Fil: Mertens, Freya. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; BélgicaFil: Gremeaux, Lies. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica; BélgicaFil: Chen, Jianghai. Huazhong University of Science and Technology. Tongji Medical College Union Hospital; China. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; BélgicaFil: Fu, Qiuli. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica. Zhejiang Provincial Key Laboratory of Ophthalmology; China. Medical College of Zhejiang University. Eye Center of the 2nd Affiliated Hospital; ChinaFil: Willems, Christophe. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; BélgicaFil: Roose, Heleen. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; BélgicaFil: Govaere, Olivier. KU Leuven. Department of Imaging and Pathology; BélgicaFil: Roskams, Tania. KU Leuven. Department of Imaging and Pathology; BélgicaFil: Cristina, Silvia Carolina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Becu Villalobos, Damasia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Joriseen, Mark. University Hospitals Leuven. Unit Head and Neck Oncology; BélgicaFil: Vander Poorten, Vincent. University Hospitals Leuven. Research Group Experimental Oto-Rhino-Laryngology, ; BélgicaFil: Bex, Marie. University Hospitals Leuven. Unit Clinical and Experimental Endocrinology; BélgicaFil: Van Loon, Johannes. University Hospitals Leuven. Research Group Experimental Neurosurgery and Neuroanatomy; BélgicaFil: Vankelecom, Hugo. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; BélgicaBioscientifica2015-04-25info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/5539Mertens, Freya; Gremeaux, Lies; Chen, Jianghai; Fu, Qiuli; Willems, Christophe; et al.; Pituitary tumors contain a side population with tumor stem cell-associated characteristics; Bioscientifica; Endocrine - Related Cancer; 22; 4; 25-4-2015; 481-5041351-00881479-6821enginfo:eu-repo/semantics/altIdentifier/url/http://erc.endocrinology-journals.org/content/22/4/481.longinfo:eu-repo/semantics/altIdentifier/doi/10.1530/ERC-14-0546info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:12:19Zoai:ri.conicet.gov.ar:11336/5539instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:12:19.662CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Pituitary tumors contain a side population with tumor stem cell-associated characteristics
title Pituitary tumors contain a side population with tumor stem cell-associated characteristics
spellingShingle Pituitary tumors contain a side population with tumor stem cell-associated characteristics
Mertens, Freya
PITUITARY
STEM CELLS
ADENOMA
MICROARRAY
CANCER STEM CELL
title_short Pituitary tumors contain a side population with tumor stem cell-associated characteristics
title_full Pituitary tumors contain a side population with tumor stem cell-associated characteristics
title_fullStr Pituitary tumors contain a side population with tumor stem cell-associated characteristics
title_full_unstemmed Pituitary tumors contain a side population with tumor stem cell-associated characteristics
title_sort Pituitary tumors contain a side population with tumor stem cell-associated characteristics
dc.creator.none.fl_str_mv Mertens, Freya
Gremeaux, Lies
Chen, Jianghai
Fu, Qiuli
Willems, Christophe
Roose, Heleen
Govaere, Olivier
Roskams, Tania
Cristina, Silvia Carolina
Becu Villalobos, Damasia
Joriseen, Mark
Vander Poorten, Vincent
Bex, Marie
Van Loon, Johannes
Vankelecom, Hugo
author Mertens, Freya
author_facet Mertens, Freya
Gremeaux, Lies
Chen, Jianghai
Fu, Qiuli
Willems, Christophe
Roose, Heleen
Govaere, Olivier
Roskams, Tania
Cristina, Silvia Carolina
Becu Villalobos, Damasia
Joriseen, Mark
Vander Poorten, Vincent
Bex, Marie
Van Loon, Johannes
Vankelecom, Hugo
author_role author
author2 Gremeaux, Lies
Chen, Jianghai
Fu, Qiuli
Willems, Christophe
Roose, Heleen
Govaere, Olivier
Roskams, Tania
Cristina, Silvia Carolina
Becu Villalobos, Damasia
Joriseen, Mark
Vander Poorten, Vincent
Bex, Marie
Van Loon, Johannes
Vankelecom, Hugo
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PITUITARY
STEM CELLS
ADENOMA
MICROARRAY
CANCER STEM CELL
topic PITUITARY
STEM CELLS
ADENOMA
MICROARRAY
CANCER STEM CELL
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Pituitary adenomas cause significant endocrine and mass-related morbidity. Little is known about the mechanisms that underlie pituitary tumor pathogenesis. In the present study, we searched for a side population (SP) in pituitary tumors representing cells with high efflux capacity and potentially enriched for tumor stem cells (TSCs). Human pituitary adenomas contain a SP irrespective of hormonal phenotype. This adenoma SP, as well as the purified SP (pSP) that is depleted from endothelial and immune cells, is enriched for cells that express ‘tumor stemness’ markers and signaling pathways, including epithelial–mesenchymal transition (EMT)-linked factors. Pituitary adenomas were found to contain self-renewing sphere-forming cells, considered to be a property of TSCs. These sphere-initiating cells were recovered in the pSP. Because benign pituitary adenomas do not grow in vitro and have failed to expand in immunodeficient mice, the pituitary tumor cell line AtT20 was further used. We identified a SP in this cell line and found it to be more tumorigenic than the non-SP ‘main population’. Of the two EMT regulatory pathways tested, the inhibition of chemokine (C-X-C motif) receptor 4 (CXCR4) signaling reduced EMT-associated cell motility in vitro as well as xenograft tumor growth, whereas the activation of TGFβ had no effect. The human adenoma pSP also showed upregulated expression of the pituitary stem cell marker SOX2. Pituitaries from dopamine receptor D2 knockout (Drd2−/−) mice that bear prolactinomas contain more pSP, Sox2+, and colony-forming cells than WT glands. In conclusion, we detected a SP in pituitary tumors and identified TSC-associated characteristics. The present study adds new elements to the unraveling of pituitary tumor pathogenesis and may lead to the identification of new therapeutic targets.
Fil: Mertens, Freya. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica
Fil: Gremeaux, Lies. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica; Bélgica
Fil: Chen, Jianghai. Huazhong University of Science and Technology. Tongji Medical College Union Hospital; China. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica
Fil: Fu, Qiuli. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica. Zhejiang Provincial Key Laboratory of Ophthalmology; China. Medical College of Zhejiang University. Eye Center of the 2nd Affiliated Hospital; China
Fil: Willems, Christophe. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica
Fil: Roose, Heleen. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica
Fil: Govaere, Olivier. KU Leuven. Department of Imaging and Pathology; Bélgica
Fil: Roskams, Tania. KU Leuven. Department of Imaging and Pathology; Bélgica
Fil: Cristina, Silvia Carolina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina
Fil: Becu Villalobos, Damasia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Joriseen, Mark. University Hospitals Leuven. Unit Head and Neck Oncology; Bélgica
Fil: Vander Poorten, Vincent. University Hospitals Leuven. Research Group Experimental Oto-Rhino-Laryngology, ; Bélgica
Fil: Bex, Marie. University Hospitals Leuven. Unit Clinical and Experimental Endocrinology; Bélgica
Fil: Van Loon, Johannes. University Hospitals Leuven. Research Group Experimental Neurosurgery and Neuroanatomy; Bélgica
Fil: Vankelecom, Hugo. Ku Leuven University (University of Leuven). Research Unit of Stem Cell Research; Bélgica
description Pituitary adenomas cause significant endocrine and mass-related morbidity. Little is known about the mechanisms that underlie pituitary tumor pathogenesis. In the present study, we searched for a side population (SP) in pituitary tumors representing cells with high efflux capacity and potentially enriched for tumor stem cells (TSCs). Human pituitary adenomas contain a SP irrespective of hormonal phenotype. This adenoma SP, as well as the purified SP (pSP) that is depleted from endothelial and immune cells, is enriched for cells that express ‘tumor stemness’ markers and signaling pathways, including epithelial–mesenchymal transition (EMT)-linked factors. Pituitary adenomas were found to contain self-renewing sphere-forming cells, considered to be a property of TSCs. These sphere-initiating cells were recovered in the pSP. Because benign pituitary adenomas do not grow in vitro and have failed to expand in immunodeficient mice, the pituitary tumor cell line AtT20 was further used. We identified a SP in this cell line and found it to be more tumorigenic than the non-SP ‘main population’. Of the two EMT regulatory pathways tested, the inhibition of chemokine (C-X-C motif) receptor 4 (CXCR4) signaling reduced EMT-associated cell motility in vitro as well as xenograft tumor growth, whereas the activation of TGFβ had no effect. The human adenoma pSP also showed upregulated expression of the pituitary stem cell marker SOX2. Pituitaries from dopamine receptor D2 knockout (Drd2−/−) mice that bear prolactinomas contain more pSP, Sox2+, and colony-forming cells than WT glands. In conclusion, we detected a SP in pituitary tumors and identified TSC-associated characteristics. The present study adds new elements to the unraveling of pituitary tumor pathogenesis and may lead to the identification of new therapeutic targets.
publishDate 2015
dc.date.none.fl_str_mv 2015-04-25
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/5539
Mertens, Freya; Gremeaux, Lies; Chen, Jianghai; Fu, Qiuli; Willems, Christophe; et al.; Pituitary tumors contain a side population with tumor stem cell-associated characteristics; Bioscientifica; Endocrine - Related Cancer; 22; 4; 25-4-2015; 481-504
1351-0088
1479-6821
url http://hdl.handle.net/11336/5539
identifier_str_mv Mertens, Freya; Gremeaux, Lies; Chen, Jianghai; Fu, Qiuli; Willems, Christophe; et al.; Pituitary tumors contain a side population with tumor stem cell-associated characteristics; Bioscientifica; Endocrine - Related Cancer; 22; 4; 25-4-2015; 481-504
1351-0088
1479-6821
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://erc.endocrinology-journals.org/content/22/4/481.long
info:eu-repo/semantics/altIdentifier/doi/10.1530/ERC-14-0546
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Bioscientifica
publisher.none.fl_str_mv Bioscientifica
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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