Acquisition of a side population fraction through downregulation of MSL3, ZNF691, VPS45, ITGB3BP, TLE2, and ZNF498 augments malignant phenotype in ovarian cancer.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE117480 | GEO | 2018/07/24
REPOSITORIES: GEO
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Project description:BACKGROUND: Therapy resistance remains one of the major challenges to improve the prognosis of patients with pancreatic cancer. Chemoresistant cells, which potentially also display cancer stem cell (CSC) characteristics, can be isolated using the side population (SP) technique. Our aim was to search for a SP in human pancreatic ductal adenocarcinoma (PDAC) and to examine its chemoresistance and CSC phenotype. RESULTS: A SP was identified in all PDAC samples, expanded and analyzed as first-generation xenografts. This SP was more resistant to gemcitabine than the other tumour cells as analyzed in vivo. Whole-genome expression profiling of the SP revealed upregulation of genes related to therapy resistance, apoptotic regulation and epithelial-mesenchymal transition. In addition, the SP displayed higher tumourigenic (CSC) activity than the other main tumour cell population (MP) as analyzed in vitro by sphere-forming capacity. CONCLUSION: We identified a SP in human PDAC and uncovered a chemoresistant and CSC-associated phenotype. This SP may represent a new therapeutic target in pancreatic cancer.
2016-01-04 | GSE36563 | GEO
Project description:BACKGROUND: Therapy resistance remains one of the major challenges to improve the prognosis of patients with pancreatic cancer. Chemoresistant cells, which potentially also display cancer stem cell (CSC) characteristics, can be isolated using the side population (SP) technique. Our aim was to search for a SP in human pancreatic ductal adenocarcinoma (PDAC) and to examine its chemoresistance and CSC phenotype. RESULTS: A SP was identified in all PDAC samples, expanded and analyzed as first-generation xenografts. This SP was more resistant to gemcitabine than the other tumour cells as analyzed in vivo. Whole-genome expression profiling of the SP revealed upregulation of genes related to therapy resistance, apoptotic regulation and epithelial-mesenchymal transition. In addition, the SP displayed higher tumourigenic (CSC) activity than the other main tumour cell population (MP) as analyzed in vitro by sphere-forming capacity. CONCLUSION: We identified a SP in human PDAC and uncovered a chemoresistant and CSC-associated phenotype. This SP may represent a new therapeutic target in pancreatic cancer. Micro-array analysis was performed on SP and MP samples of 5 xenografts, grown from 5 different human PDAC samples.
2016-01-04 | E-GEOD-36563 | 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.
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:The identification and characterization of subpopulations of cancer stem cells (CSCs) provide new understandings and possible therapeutic implications in cancer biology. We found the ovarian cancer sphere cells possessed CSCs properties maintained self renewal, drug resistance, and tumorigenesis. Using high-throughput microarray system, we identified common GO terms and pathway signatures significantly enriched in ovarian and breast cancer stem cells. Ovarian and breast cancer cells were cultured in sphere formation conditions, and total RNA from those spheres and conresponding adhered cell was hybridized on Affymetrix microarrays.
2013-11-25 | E-GEOD-43657 | biostudies-arrayexpress
Project description:Glioblastoma is one of the deadliest malignancies worldwide and is virtually incurable due to its highly infiltrative growth and limited sensitivity to conventional treatment by radiochemotherapy. It is hypothesized that a small population of cells with a stem-like phenotype is the major culprit of tumor recurrence. These cells are characterized by an enhanced DNA repair capacity and expression of stemness marker genes, and elimination of this population might delay or even stop tumor recurrence following radiochemotherapy. The aim of this study was to analyze whether interference with the Hedgehog signaling (Hh) pathway or combined Hh/Notch blockade can efficiently target these cancer stem cells and sensitize them to chemotherapeutic drugs. Using tumor sphere lines and primary glioma cells we demonstrate that the Hh pathway inhibitor GANT61 (GANT) and the Hh/Notch inhibitor arsenic trioxide (ATO) are capable to synergistically decrease proliferation and induce cell death in combination with the natural cotton derived anticancer agent (-)-Gossypol (Gos). In contrast to GANT in combination with Gos, the ATO/Gos combination also strongly prevented sphere formation and recovery. These synergistic effects were associated with major proteomic changes indicating decreased cell movement, distortion of cell cycle and DNA repair, as well as markedly reduced stemness. Collectively, our data show that ATO and Gos, two drugs that are safe for use in humans, represent a promising targeted therapy approach for the synergistic and specific elimination of glioma stem-like cells.
2019-03-13 | PXD009249 | Pride
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:Msl3 is a member of the chromatin-associated male-specific lethal MSL complex which is responsible for the transcriptional upregulation of genes on the X chromosome in males Drosophila. Although the dosage complex operates differently in mammals, the Msl3 gene is conserved from flies to humans. Msl3 is required for meiotic entry during Drosophila oogenesis. Recent reports indicate that also in primates, Msl3 is expressed in undifferentiated germline cells before meiotic entry. However, if Msl3 plays a role in the meiotic entry of mammals has yet to be explored. To study this, we used mouse spermatogenesis as a study model. Analyses of single cells RNA-seq data revealed that in mouse, differently from what was reported in primates, Msl3 is expressed in meiotic cells. To test the role of Msl3 in meiosis, we used a male germline-specific Stra8-iCre driver and a newly generated Msl3flox conditional knock-out mouse line. Msl3 conditional loss-of-function in spermatogonia did not cause spermatogenesis defects or changes in the expression of genes related to meiosis. Our data suggest that, in mice, Msl3 exhibits delayed expression compared to Drosophila and primates, and loss-of-function mutations disrupting the chromodomain or the MRG domain of Msl3 alone do not impede meiotic entry in rodents.
2023-10-05 | GSE235777 | GEO
Project description:Melanoma remains the most lethal skin cancer, mainly because of high resistance to therapy. Side population (SP) cells are found in many types of cancer and are usually enriched in therapy-resistant as well as tumorigenic cells. Here, we identified a Hoechst dye-effluxing SP in a large series of human melanoma samples representing different progression phases. The SP size did not change with disease stage but was correlated with the prognostic “Breslow’s depth” in the primary (cutaneous) tumors. When injected into immunodeficient mice, the SP generated larger tumors than the bulk “main population” (MP) melanoma cells in two consecutive generations, and showed tumorigenic capacity at lower cell numbers than the MP. In addition, the SP reconstituted the heterogeneous composition of the human A375 melanoma cell line, and its clonogenic activity was 2.5-fold higher than that of the MP. Gene-expression analysis revealed upregulated expression in the melanoma SP (versus the MP) of genes associated with chemoresistance and anti-apoptosis. Consistent with these molecular characteristics, the SP increased in proportion when A375 cells were exposed to the melanoma standard chemotherapeutic agent dacarbazine, and to the aggravating condition of hypoxia. In addition, the SP showed enhanced expression of genes related to cell invasion and migration, as well as to putative (melanoma) cancer stem cells (CSC) including ABCB1 and JARID1B. ABCB1 immunoreactivity was detected in a number of tumor cells in human melanomas, and in particular in clusters at the invasive front of the primary tumors. Together, our findings support that the human melanoma SP is enriched in tumorigenic and chemoresistant capacity, considered key characteristics of CSC. The melanoma SP may therefore represent an interesting therapeutic target. Four primary melanomas (subtype SSMM) were dissociated into single cells. From each of these single cell suspensions, side population (SP) and bulk \main population\ (MP) cells were isolated based on their Hoechst-effluxing capability using fluorescence-activated cell sorting. Gene expression of SP cells is analyzed relative to the gene expression of the corresponding MP cells.
2014-05-27 | E-GEOD-48838 | biostudies-arrayexpress