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

2016 ◽  
Author(s):  
Freya Mertens ◽  
Lies Gremeaux ◽  
Jianghai Chen ◽  
Qiuli Fu ◽  
Christophe Williems ◽  
...  
Keyword(s):  
Stem Cell ◽  
Side Population ◽  
Pituitary Tumors ◽  
Tumor Stem Cell

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

2015 ◽  
Vol 22 (4) ◽  
pp. 481-504 ◽  
Author(s):  
Freya Mertens ◽  
Lies Gremeaux ◽  
Jianghai Chen ◽  
Qiuli Fu ◽  
Christophe Willems ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Line ◽  
Pituitary Adenomas ◽  
Pituitary Tumor ◽  
Side Population ◽  
Pituitary Tumors ◽  
Stem Cell Marker ◽  
Tumor Stem Cell ◽  
Tumor Pathogenesis

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.

scholarly journals Side Population Does Not Define Stem Cell-Like Cancer Cells in the Adrenocortical Carcinoma Cell Line NCI h295R

Endocrinology ◽  
2007 ◽  
Vol 149 (3) ◽  
pp. 1314-1322 ◽  
Author(s):  
Urs D. Lichtenauer ◽  
Igor Shapiro ◽  
Klaus Geiger ◽  
Marcus Quinkler ◽  
Martin Fassnacht ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Line ◽  
Cell Population ◽  
Side Population ◽  
Primary Cultures ◽  
Regulatory Protein ◽  
Cytotoxic Agents ◽  
Tumor Stem Cell ◽  
Proliferative Potential ◽  
Tumor Entities

Recent evidence suggests the existence of a stem cell-like subpopulation of cells in hematological and solid tumor entities, which determine the malignant phenotype of a given tumor through their proliferative potential and chemotherapy resistance. A recently used technique for the isolation of this cell population is through exclusion of the vital dye Hoechst 33342, which defines the so-called side population (SP). Herein we demonstrate the presence of SP cells in a variety of adrenal specimens, including primary cultures of human adrenocortical tumors and normal adrenal glands as well as established human and murine adrenocortical cancer cell lines by fluorescence-activated cell sorter analysis and confocal microscopy. On a functional level, SP cells from the human adrenocortical tumor cell line NCI h295R revealed an expression pattern consistent with a less differentiated phenotype, including lower expression of steroidogenic enzymes such as steroid acute regulatory protein (StAR) and side-chain cleavage enzyme (P450scc) in comparison with non-SP cells. However, proliferation between SP and non-SP cells did not differ (105.6 ± 18.1 vs. 100.0 ± 3.5%). Furthermore, re-sorting and tracing experiments revealed the capacity for both cell types to give rise to the original SP- and non-SP-containing cell population. Similarly to the baseline growth kinetics, no survival benefit was evident in SP cells after treatment with cytotoxic agents commonly used in adrenocortical carcinomas. Taken together, these findings provide evidence that Hoechst dye exclusion, in contrast to what has been reported for other tumor entities, is not a major tumor stem cell defining marker in adrenocortical NCI h295R tumor cells.

Side population in oral squamous cell carcinoma possesses tumor stem cell phenotypes

2009 ◽  
Vol 277 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Ping Zhang ◽  
Yan Zhang ◽  
Li Mao ◽  
Zhiyuan Zhang ◽  
Wantao Chen
Keyword(s):  
Squamous Cell Carcinoma ◽  
Stem Cell ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Side Population ◽  
Tumor Stem Cell ◽  
Cell Phenotypes

Vitamin C deficient reduces proliferation in a human periventricular tumor stem cell‐derived glioblastoma model

2021 ◽  
Author(s):  
Nery Jara ◽  
Eder Ramirez ◽  
Luciano Ferrada ◽  
Katterine Salazar ◽  
Francisca Espinoza ◽  
...  
Keyword(s):  
Stem Cell ◽  
Vitamin C ◽  
Tumor Stem Cell

scholarly journals Semaphorin 3A mediated brain tumor stem cell proliferation and invasion in EGFRviii mutant gliomas

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Dominique M. O. Higgins ◽  
Maisel Caliva ◽  
Mark Schroeder ◽  
Brett Carlson ◽  
Pavan S. Upadhyayula ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cell ◽  
Brain Tumor ◽  
Propidium Iodide ◽  
Tumor Stem Cell ◽  
Semaphorin 3A ◽  
Brain Tumor Stem Cell ◽  
Proliferation And Invasion ◽  
Invasion Assays

Abstract Background Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, with a median survival of approximately 15 months. Semaphorin 3A (Sema3A), known for its axon guidance and antiangiogenic properties, has been implicated in GBM growth. We hypothesized that Sema3A directly inhibits brain tumor stem cell (BTSC) proliferation and drives invasion via Neuropilin 1 (Nrp1) and Plexin A1 (PlxnA1) receptors. Methods GBM BTSC cell lines were assayed by immunostaining and PCR for levels of Semaphorin 3A (Sema3A) and its receptors Nrp1 and PlxnA1. Quantitative BrdU, cell cycle and propidium iodide labeling assays were performed following exogenous Sema3A treatment. Quantitative functional 2-D and 3-D invasion assays along with shRNA lentiviral knockdown of Nrp1 and PlxnA1 are also shown. In vivo flank studies comparing tumor growth of knockdown versus control BTSCs were performed. Statistics were performed using GraphPad Prism v7. Results Immunostaining and PCR analysis revealed that BTSCs highly express Sema3A and its receptors Nrp1 and PlxnA1, with expression of Nrp1 in the CD133 positive BTSCs, and absence in differentiated tumor cells. Treatment with exogenous Sema3A in quantitative BrdU, cell cycle, and propidium iodide labeling assays demonstrated that Sema3A significantly inhibited BTSC proliferation without inducing cell death. Quantitative functional 2-D and 3-D invasion assays showed that treatment with Sema3A resulted in increased invasion. Using shRNA lentiviruses, knockdown of either NRP1 or PlxnA1 receptors abrogated Sema3A antiproliferative and pro-invasive effects. Interestingly, loss of the receptors mimicked Sema3A effects, inhibiting BTSC proliferation and driving invasion. Furthermore, in vivo studies comparing tumor growth of knockdown and control infected BTSCs implanted into the flanks of nude mice confirmed the decrease in proliferation with receptor KD. Conclusions These findings demonstrate the importance of Sema3A signaling in GBM BTSC proliferation and invasion, and its potential as a therapeutic target.

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