Pituitary tumors contain a side population with tumor stem cell-associated characteristics
| Autor: | Qiuli Fu, Lies Gremeaux, Carolina Cristina, Marie Bex, Johannes van Loon, Hugo Vankelecom, Heleen Roose, Damasia Becu-Villalobos, Jianghai Chen, Tania Roskams, Christophe Willems, Olivier Govaere, Mark Jorissen, Freya Mertens, Vincent Vander Poorten |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Cancer Research Endocrinology Diabetes and Metabolism Mice SCID Stem cell marker Receptors Dopamine CANCER STEM CELL Endocrinology Aged 80 and over Mice Knockout education.field_of_study Patología purl.org/becyt/ford/3.1 [https] Middle Aged Medicina Básica Oncology Pituitary Gland Neoplastic Stem Cells purl.org/becyt/ford/3 [https] Female Stem cell Adenoma Adult medicine.medical_specialty CIENCIAS MÉDICAS Y DE LA SALUD Population Transplantation Heterologous Biology Cell Line Young Adult MICROARRAY SOX2 Side population Cancer stem cell PITUITARY Internal medicine medicine Animals Humans Pituitary Neoplasms education Aged Gene Expression Profiling SOXB1 Transcription Factors Pituitary tumors medicine.disease ADENOMA Mice Inbred C57BL Cancer research STEM CELLS |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| ISSN: | 1479-6821 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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