Pituitary tumors contain a side population with 'tumor stem cell'-associated characteristics.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE62960 | GEO | 2015/08/04
SECONDARY ACCESSION(S): PRJNA266292
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-08-04 | E-GEOD-62960 | biostudies-arrayexpress
Project description: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.
2015-08-04 | GSE62866 | GEO
Project description: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 9 human pituitary adenoma samples (5 x NF-A; 4 x GH-A). 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, total SP and MP cells were sorted by FACS. Separate assays were run subsequently for the two fractions. As such we present data from 18 microarrays.
2015-08-04 | E-GEOD-62866 | biostudies-arrayexpress
Project description: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.
2015-08-04 | GSE62870 | GEO
Project description: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.
2015-08-04 | E-GEOD-62870 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-01-30 | GSE123610 | GEO
Project description:IntroductionWhether cancer stem cells occur in BRCA1-associated breast cancer and contribute to therapeutic response is not known.MethodsWe generated and characterized 16 cell lines from five distinct Brca1deficient mouse mammary tumors with respect to their cancer stem cell characteristics.ResultsAll cell lines derived from one tumor included increased numbers of CD44+/CD24- cells, which were previously identified as human breast cancer stem cells. All cell lines derived from another mammary tumor exhibited low levels of CD44+/CD24- cells, but they harbored 2% to 5.9% CD133+ cells, which were previously associated with cancer stem cells in other human and murine tumors. When plated in the absence of attachment without presorting, only those cell lines that were enriched in either stem cell marker formed spheroids, which were further enriched in cells expressing the respective cancer stem cell marker. In contrast, cells sorted for CD44+/CD24- or CD133+ markers lost their stem cell phenotype when cultured in monolayers. As few as 50 to 100 CD44+/CD24- or CD133+ sorted cells rapidly formed tumors in nonobese diabetic/severe combined immunodeficient mice, whereas 50-fold to 100-fold higher numbers of parental or stem cell depleted cells were required to form few, slow-growing tumors. Expression of stem cell associated genes, including Oct4, Notch1, Aldh1, Fgfr1, and Sox1, was increased in CD44+/CD24- and CD133+ cells. In addition, cells sorted for cancer stem cell markers and spheroid-forming cells were significantly more resistant to DNA-damaging drugs than were parental or stem cell depleted populations, and they were sensitized to the drugs by the heat shock protein-90 inhibitor 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride).ConclusionBrca1-deficient mouse mammary tumors harbor heterogeneous cancer stem cell populations, and CD44+/CD24- cells represent a population that correlates with human breast cancer stem cells.
| S-EPMC2374965 | biostudies-literature
Project description:The most common type of pituitary neoplasms is benign pituitary adenoma (PA). Clinically significant PAs affect around 0.1% of the population. Currently, there is no established human PA cell culture available and when PA tumor cells are cultured they form two distinct types depending on culturing conditions either free-floating aggregates also known as pituispheres or cells adhering to the surface of cell plates and displaying mesenchymal stem-like properties. The aim of this study was to trace the origin of sphere-forming and adherent pituitary cell cultures and characterize the potential use of these surgery derived cell lines as PA model. We carried out a paired-end exome sequencing of patients' tumor and germline DNA using Illumina NextSeq followed by characterization of corresponding PA cell cultures. Variation analysis revealed a low amount of somatic mutations (mean = 5.2, range 3-7) in exomes of PAs. Somatic mutations of the primary surgery material can be detected in the exomes of respective pituispheres, but not in exomes of respective mesenchymal stem-like cells. For the first time, we show that the genome of pituispheres represents genome of PA while mesenchymal stem cells derived from the PA tissue do not contain mutations characteristic to PA in their genome, therefore, most likely representing normal cells of pituitary or surrounding tissues. This finding indicates that pituispheres can be used as a human model of PA cells, but combination of cell culturing techniques and NGS needs to be employed to adjust for disability to propagate spheres in culturing conditions.
| S-EPMC7256168 | biostudies-literature
Project description:Cancer stem cells (CSC) are believed to be involved in tumor evasion of classical antitumor therapies and have thus become an attractive target for further improvement of anticancer strategies. However, the existence and identity of CSC are still a matter of controversy. In a systematic screen of 13 ovarian cancer cell lines we show that cells with stem cell properties are reliably detectable as a minor population, characterized by ABC transporter expression resulting in the side population (SP) phenotype. In different cell lines, either ABCG2 or ABCB1 was found to be responsible for this effect. Purified SP cells featured virtually all characteristics of bona fide CSC, including clonogenicity, asymmetric division and high tumorigenicity in vivo. Using in-depth phenotyping by multicolor flow cytometry, we found that among the investigated ovarian cancer cell lines the SP compartment exhibits tremendous heterogeneity and is composed of multiple phenotypically distinct subpopulations. Thus, our study confirms previous results showing that CSC are contained within the SP. However, the exact identity of the CSC is still disguised by the high complexity of the CSC-containing compartment. Further functional studies are needed to determine whether a single cellular subset can unambiguously be defined as CSC or whether multiple stem cell-like cells with different properties coexist. Moreover, the observed heterogeneity may reflect a high level of plasticity and likely influences tumor progression, escape from immune-surveillance and development of resistance to anticancer therapies and should therefore be considered in the development of new treatment strategies.
| S-EPMC4196181 | biostudies-other
Project description:Over the course of pregnancy, the human uterus undergoes a 500- to 1,000-fold increase in volume and a 24-fold increase in weight. The uterine smooth muscle layer or myometrium is remodeled, and both cell hypertrophy and hyperplasia are evident. The origin of the new smooth muscle cells, however, is unclear. They may arise from existing smooth muscle cells, or they may be the product of stem cell differentiation. This study describes a subset of myometrial cells isolated from nonpregnant human myometrium that represents the myometrial stem cell population. This was characterized as side population of myometrial cells (myoSP) by a distinct Hoechst dye efflux pattern. In contrast to the main population of myometrial cells (myoMP), myoSP resided in quiescence, underexpressed or lacked myometrial cell markers, and could proliferate and eventually differentiate into mature myometrial cells in vitro only under low oxygen concentration. Although myoMP displayed mature myometrial phenotypes before and after in vitro cultivation, only myoSP, not myoMP, generated functional human myometrial tissues efficiently when transplanted into the uteri of severely immunodeficient mice. Finally, myoSP were multipotent and made to differentiate into osteocytes and adipocytes in vitro under the appropriate differentiation-inducing conditions. Thus, myoSP exhibited phenotypic and functional characteristics of myometrial stem cells. Study of myoSP will improve the understanding of myometrial physiology and the pathogenesis of myometrium-derived diseases such as leiomyoma. myoSP may also represent a novel source of biological material that could be used in the reconstruction of not only the human uterus but also other organs as well.
| S-EPMC2141840 | biostudies-other