LGR5 positivity defines stem-like cells in colorectal cancer [Expression]
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ABSTRACT:
PROVIDER: PRJNA198024 | ENA |
REPOSITORIES: ENA
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Project description:To further elucidate the role of the intestinal stem cell marker Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) in colorectal cancer (CRC), we exposed Lgr5-EGFP-IRES-Cre-ERT2 mice to azoxymethane/dextrane sodium sulfate (AOM/DSS) which induces inflammation-driven colon tumors. Tumors were then flow-sorted into fractions of epithelial cells that expressed high or low levels of Lgr5 and were characterized using gene expression profiling. In the AOM/DSS-induced mouse colon tumors Lgr5 high cells showed higher levels of several stem cell-associated genes and higher Wnt signaling than Lgr5 low tumor cells and Lgr5 high normal colon epithelial cells. To further elucidate the role of the intestinal stem cell marker Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) in colorectal cancer (CRC), we transduced SW480 CRC cells with lentiviral shRNA constructs to silence LGR5 expression. This resulted in a depletion of spheres but did not affect adherently growing cells. Spheres expressed higher levels of several stem cell-associated genes than adherent cells. Notch signaling was down-regulated upon LGR5 silencing. This was confirmed by immunohistochemistry against cleaved NOTCH1. Normal mouse colons and AOM/DSS-induced mouse colon tumors were flow-sorted into Lgr5 high and low cells before gene expression was measured. Fifteen independent experiments were performed using seven individual mice for normal colons and eight for tumors. Appropriate LGR5 status was confirmed by real-time qRT-PCR before measuring silencing induced gene expression. Three independent experiments were performed for each cell fraction using separately cultured cells for each experiment.
2013-04-19 | E-GEOD-46200 | biostudies-arrayexpress
Project description:To further elucidate the role of the intestinal stem cell marker Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) in colorectal cancer (CRC), we exposed Lgr5-EGFP-IRES-Cre-ERT2 mice to azoxymethane/dextrane sodium sulfate (AOM/DSS) which induces inflammation-driven colon tumors. Tumors were then flow-sorted into fractions of epithelial cells that expressed high or low levels of Lgr5 and were characterized using gene expression profiling. In the AOM/DSS-induced mouse colon tumors Lgr5 high cells showed higher levels of several stem cell-associated genes and higher Wnt signaling than Lgr5 low tumor cells and Lgr5 high normal colon epithelial cells. To further elucidate the role of the intestinal stem cell marker Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) in colorectal cancer (CRC), we transduced SW480 CRC cells with lentiviral shRNA constructs to silence LGR5 expression. This resulted in a depletion of spheres but did not affect adherently growing cells. Spheres expressed higher levels of several stem cell-associated genes than adherent cells. Notch signaling was down-regulated upon LGR5 silencing. This was confirmed by immunohistochemistry against cleaved NOTCH1.
2013-04-19 | GSE46200 | GEO
Project description:Lgr5-EGFP-IRES-Cre-ERT2 mice were exposed to azoxymethane/dextrane sodium sulfate (AOM/DSS) which induces inflammation-driven colon tumors. Tumors were then flow-sorted into fractions of epithelial cells that expressed high or low levels of Lgr5. To exclude that transcriptional differences between Lgr5 high and low mouse colon tumor cells were imposed by distinct patterns of chromosomal aberrations in the two cell fractions, we also performed array comparative genomic hybridization (aCGH) from these tumors. All eight analyzed tumors were chromosomally stable, and thus, no difference between Lgr5 high and low cells could be detected. AOM/DSS-induced mouse colon tumors were flow-sorted into Lgr5 high and low cells before aCGH was performed. Biological replicates: 8. Two CGH array platforms.
2013-05-07 | E-GEOD-46711 | biostudies-arrayexpress
Project description:Lgr5-EGFP-IRES-Cre-ERT2 mice were exposed to azoxymethane/dextrane sodium sulfate (AOM/DSS) which induces inflammation-driven colon tumors. Tumors were then flow-sorted into fractions of epithelial cells that expressed high or low levels of Lgr5. To exclude that transcriptional differences between Lgr5 high and low mouse colon tumor cells were imposed by distinct patterns of chromosomal aberrations in the two cell fractions, we also performed array comparative genomic hybridization (aCGH) from these tumors. All eight analyzed tumors were chromosomally stable, and thus, no difference between Lgr5 high and low cells could be detected.
2013-05-07 | GSE46711 | GEO
Project description:Like normal colorectal epithelium, colorectal carcinomas (CRCs) are organized hierarchically and include populations of cells with stem-like properties. Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) is associated with these stem cells in normal colorectal epithelium; however, the precise function of LGR5 in CRC remains largely unknown. Here, we analyzed the functional and molecular consequences of short hairpin RNA-mediated silencing of LGR5 in CRC cell lines SW480 and HT-29. Additionally, we exposed Lgr5-EGFP-IRES-CreERT2 mice to azoxymethane/dextrane sodium sulfate (AOM/DSS), which induces inflammation-driven colon tumors. Tumors were then flow-sorted into fractions of epithelial cells that expressed high or low levels of Lgr5 and were molecularly characterized using gene expression profiling and array comparative genomic hybridization. Silencing of LGR5 in SW480 CRC cells resulted in a depletion of spheres but did not affect adherently growing cells. Spheres expressed higher levels of several stem cell-associated genes than adherent cells, including LGR5. Silencing of LGR5 reduced proliferation, migration and colony formation in vitro and tumorigenicity in vivo. In accordance with these results, NOTCH signaling was downregulated upon LGR5 silencing. In AOM/DSS-induced colon tumors, Lgr5 high cells showed higher levels of several stem cell-associated genes and higher Wnt signaling than Lgr5 low tumor cells and Lgr5 high normal colon cells. Array comparative genomic hybridization revealed no genomic imbalances in either tumor cell fraction. Our data elucidate mechanisms that define the role of LGR5 as a marker for stem-like cells in CRC.
| S-EPMC3977143 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-05-07 | E-GEOD-46712 | biostudies-arrayexpress
Project description:LGR5 positivity defines stem-like cells in colorectal cancer [aCGH]
| PRJNA202103 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2013-05-07 | GSE46712 | GEO
Project description:Colorectal cancer tumors are composed of heterogeneous and plastic cell populations, including a pool of cancer stem cells that express LGR5. Whether these distinct cell populations display different mechanical properties, and how these properties might contribute to metastasis is unknown. Using CRC patient derived organoids (PDOs), we found that compared to LGR5- cells, LGR5+ cancer stem cells are stiffer, adhere better to the extracellular matrix (ECM), move slower both as single cells and clusters, display higher nuclear YAP, show a higher survival rate in response to mechanical confinement, and form larger transendothelial gaps. These differences are largely explained by the downregulation of the membrane to cortex attachment proteins Ezrin/Radixin/Moesin (ERMs) in the LGR5+ cells. By analyzing scRNA-seq expression patterns from a patient cohort, we show that this downregulation is a robust signature of colorectal tumors. Our results show that LGR5- cells display a mechanically dynamic phenotype suitable for dissemination from the primary tumor whereas LGR5+ cells display a mechanically stable and resilient phenotype suitable for extravasation and metastatic growth.
2023-12-20 | GSE247359 | GEO