Transcriptomics

Dataset Information

36

Pituitary tumors contain a (CD31¯/CD45¯ purified) side population with 'tumor stem cell'-associated characteristics [set 2]


ABSTRACT: Pituitary adenomas cause significant endocrine and mass-related morbidity. Not much is known about mechanisms underlying pituitary tumor pathogenesis. We searched for a side population (SP) in pituitary tumor, representing cells with high efflux capacity and potentially enriching for cancer/tumor stem cells (CSC/TSC). Human pituitary adenomas contain a SP irrespective of hormonal phenotype. This adenoma SP, as well as the further purified SP (pSP) depleted from endothelial and immune cells, enriches for cells that express ‘tumor stemness’ markers and signaling pathways, including epithelial-mesenchymal transition (EMT)-linked factors. The adenomas were found to contain self-renewing sphere-forming cells, considered a property of TSC. The sphere-initiating cells were retrieved in the pSP. Because benign pituitary adenomas do not grow in vitro and 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 more tumorigenic than the main population (MP). Of the two EMT-regulatory pathways tested, inhibition of Cxcr4 signaling reduced EMT-linked cell motility in vitro as well as xenograft tumor growth, whereas activation of TGFβ had no effect. The tumor pSP showed upregulated expression of the pituitary stem cell marker SOX2. Pituitaries from dopamine receptor D2 knockout (Drd2-/-) mice bearing prolactinomas, contain more pSP, Sox2+ and colony-forming cells than wildtype glands. In conclusion, we detected a SP in pituitary tumors and identified TSC-associated characteristics. Our study may contribute to a better understanding of pituitary tumor pathogenesis and lead to new therapeutic targets. We determined gene expression profiles for 5 human pituitary adenoma samples (all NF-A type). The samples were obtained immediately after transsphenoidal resection (by the neurosurgeon Dr. van Loon, Division Neurosurgery, University Hospitals Leuven). Informed consent was received from the patients. Hormonal phenotype was determined by the Department of Imaging and Pathology (University Hospitals Leuven). For each sample, CD31¯/CD45¯ SP (purified SP or pSP) and pMP cells were sorted by FACS. Separate assays were run subsequently for the two fractions. As such we present data from 10 microarrays.

ORGANISM(S): Homo sapiens  

SUBMITTER: Heleen Roose  Johannes van Loon   Qiuli Fu   Carolina Cristina   Wouter Van Delm   Olivier Govaere   Lies Gremeaux   Hugo Vankelecom   Christophe Willems   Marie Bex   Damasia Becú-Villalobos   Freya Mertens   Jianghai Chen   Tania Roskams    

PROVIDER: E-GEOD-62870 | ArrayExpress | 2015-08-19

SECONDARY ACCESSION(S): GSE62870PRJNA266101

REPOSITORIES: GEO, ArrayExpress

altmetric image

Publications


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 im  ...[more]

Similar Datasets

2015-09-21 | E-GEOD-62866 | ArrayExpress
2014-10-05 | E-GEOD-42404 | ArrayExpress
2011-06-10 | E-GEOD-4237 | ArrayExpress
2006-02-14 | GSE4237 | GEO
2016-02-22 | E-GEOD-77517 | ArrayExpress
2013-06-17 | E-GEOD-46311 | ArrayExpress
2012-06-25 | E-GEOD-32375 | ArrayExpress
| GSE93825 | GEO
| GSE89779 | GEO
2016-12-28 | E-GEOD-67788 | ArrayExpress