Differential gene expression profiles of side population and non-side population cells of malignant pleural mesothelioma
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: naimei tang
PROVIDER: E-GEOD-33734 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Malignant pleural mesothelioma (MPM), which is associated with occupational asbestos exposure, is a deadly disease with no effective treatments due mainly to its high resistance to anti-cancer drugs. The molecular mechanisms responsible for its chemotherapeutic resistance are complicated and undefined. However, the presence of side population cells (SP cells) in tumors is a well-accepted explanation for their anti-cancer drug resistance. To identify SP cell-specific gene expression signature, microarray technique has been employed. Our data show differential gene expression profiles between SP and non-SP cells of H2714 mesothelioma cells. SP cells over-expressed genes associated with cancer stem cell (CSC) and drug resistance: DUSP6, SPRY2 and IL6, as well as multi-pathways, including the cancer stem cell-associated pathways Notch and c-Kit. Therefore, we believe that targeting CSC-specific genes and pathways in SP cells may hold the key to the discovery of effective treatments for reversing chemotherapeutic resistance to MPM treatment.
2011-11-18 | GSE33734 | 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.
2016-01-04 | GSE36563 | 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.
2014-05-27 | GSE48838 | 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
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:Purpose: To explore the side population (SP) in pancreatic ductal adenocarcinoma (PDAC) for its gene expression profile and its association to cancer stem cells (CSC) and to evaluate the value of genes from its gene signature on patient survival. Experimental design: Side and main population (MP) cells were isolated from 11 human PDAC resection specimens using fluorescence-activated cell sorting (FACS) after Hoechst incubation. Total RNA was extracted for whole-genome analysis. A gene signature for the purified SP (pSP; depleted from immune/endothelial CD45+/CD31+ cells) was developed and validated with the nCounter system on expression data of 78 primary PDAC using Cox regression analyses for disease-free and overall survival. Results: An SP was identified in all PDAC samples. Whole-genome expression profiling of pSP revealed upregulation of genes related to therapy-resistance and of CSC-associated genes and pathways. A pSP signature of 32 up- or downregulated genes was capable of discriminating SP from MP in an independent set of 10 PDAC samples, and some contributing genes had a prognostic value in a separate series of 78 patients who underwent surgery for PDAC. Conclusion: Pancreatic cancer contains an SP with chemo-resistant and CSC-associated molecular characteristics. Genes from a newly defined pSP gene signature are related to survival of patients who undergo surgical resection for pancreatic cancer, and might therefore represent potential therapeutic targets. Microarray analysis was performed on SP and MP samples from 11 different human PDAC samples.
2014-09-26 | E-GEOD-42404 | biostudies-arrayexpress
Project description:Intratumoral heterogeneity is a major barrier against effective cancer therapy. Human malignant mesothelioma (HMM) that is closely associated with asbestos exposure is extremely heterogeneous in morphology and molecular phenotype. Contrast to genetic mutations, the role of epigenetic modifications in the generation and maintenance of heterogeneous populations in cancers remains largely undetermined. The present study was performed to investigate underlying molecular mechanisms for the emergence of intratumoral heterogeneity by identifying the global microRNA expression profile of distinct subpopulations of MS1 cell line, a HMM cell line. More aggressive cancer cells could be enriched by side population (SP) assay in HMM [20]. The sorted SP and NSP subpopulations were subjected to the microarray analysis of miRNA expression to investigate differentially altered miRNA genes defining tumor heterogeneity in HMM. Total RNAs were isolated from the sorted subpopulations of HMM cells, SP and non-SP fractions. The expression profile of miRNAs was evaluated using Affymetrix GeneChip miRNA Arrays. After data extraction and normalization, the microRNAs defining the cell subpopulations were determined using bioinformatics softwares. A total of 95 miRNAs including 42 up-regulated and 53 down-regulated were identified based on the criteria of 2 fold difference and a p-value < 0.05. Functional ontology of the dysregulated miRNAs revealed that a large number of target genes were categorized into the regulation of various cellular processes, including cell proliferation, programmed cell death, cell migration, cellular response to stress, and stem cell maintenance. The data show that microRNAs are significantly involved in the generation and maintenance of intratumoral heterogeneity and their regulation could be an effective strategy to eradicate a more aggressive cancer cell subpopulation. This is the first to report the profile of miRNA expression in CSCs in HMM by using side population assay assisted with flow cytometry. It will be valuable to understand the regulatory function of HMM CSC miRNAs in generation and maintenance of intratumoral heterogeneity. Total RNAs were isolated from the sorted subpopulations of HMM cells, SP and non-SP fractions. (no replicates)
2016-06-15 | E-GEOD-69910 | biostudies-arrayexpress
Project description:Immature cell populations, including stem cells and progenitor cells, can be found in M-bM-^@M-^\side-population (SP)M-bM-^@M-^] cells. Although SP cells isolated from some adult tissues have been reported elsewhere, isolation and characterization of human trophoblast SP cells remained to be reported. We used microarrays to detail the global program of gene expression underlying cell differentiation and identified up-regulated genes of SP HTR-8/SVneo SP cells or NSP cells were isolated using a FACS Vantage fluorescence-activated cell sorter (BD Bioscience, San Jose, California) using dual wavelength analysis (blue, 424 - 444nm; red 675 nm) after excitation with 350 nm UV light. PI-positive dead cells were excluded from the analysis. Sorted SP and NSP cells' RNA had been analyzed by microarray analysis.
2014-09-18 | E-GEOD-61547 | biostudies-arrayexpress
Project description:We are currently studying the mechanisms that confer tumour initiating potential upon SP, and as part of this work, we undertook gene profiling studies comparing expression between SP and non-SP cells, initially focusing on the most common soft tissue sarcoma, malignant fibrous histiocytoma (or MFH) Sarcomas contain a subpopulation of cells which exclude Hoechst dye (SP cells) and are enriched for tumor initiating potential. The persistence of SP cells could be responsible for relapse or a failed response to therapy. Expression profiles were compared between the SP and non-SP cells from malignant fibrous histiocytoma (MFH) tumors using microarray. The Hedgehog and Notch pathways were activated in SP cells. Blocking these pathways in MFH xenografts established in NOD-SCID mice depleted the abundance of SP cells and reduced tumor growth. Intriguingly, treatment also substantially inhibited the potential for successful secondary transplantation. The data provides support that SP cells act as tumor initiating cells in sarcomas and suggests targeting the SP as an enticing approach for sarcoma therapy. In this study, we studied six MFH tumours, and identified a number of signaling pathways that were consistently activated in the SP population compared to the non-SP population.
2012-01-17 | E-GEOD-32375 | biostudies-arrayexpress
Project description:Purpose: To explore the side population (SP) in pancreatic ductal adenocarcinoma (PDAC) for its gene expression profile and its association to cancer stem cells (CSC) and to evaluate the value of genes from its gene signature on patient survival. Experimental design: Side and main population (MP) cells were isolated from 11 human PDAC resection specimens using fluorescence-activated cell sorting (FACS) after Hoechst incubation. Total RNA was extracted for whole-genome analysis. A gene signature for the purified SP (pSP; depleted from immune/endothelial CD45+/CD31+ cells) was developed and validated with the nCounter system on expression data of 78 primary PDAC using Cox regression analyses for disease-free and overall survival. Results: An SP was identified in all PDAC samples. Whole-genome expression profiling of pSP revealed upregulation of genes related to therapy-resistance and of CSC-associated genes and pathways. A pSP signature of 32 up- or downregulated genes was capable of discriminating SP from MP in an independent set of 10 PDAC samples, and some contributing genes had a prognostic value in a separate series of 78 patients who underwent surgery for PDAC. Conclusion: Pancreatic cancer contains an SP with chemo-resistant and CSC-associated molecular characteristics. Genes from a newly defined pSP gene signature are related to survival of patients who undergo surgical resection for pancreatic cancer, and might therefore represent potential therapeutic targets.
2014-09-26 | GSE42404 | GEO