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Expression data from colon fibroblasts treated with Sonic hedgehog homolog (SHH)

ABSTRACT: Canonical Hedgehog (Hh) signaling regulates the expression of genes that are critical to the patterning and development of a variety of organ systems. In adult, both ligand-dependent and ligand-independent Hh pathway activation are known to promote tumorigenesis. Recent studies have shown that in tumors promoted by Hh ligand, activation occurs within the stromal microenvironment (Yauch et al., 2009). In situ hybridization of the pathway target gene, Ptch1, shows that signaling is located at stromal perivascular fibroblast-like cells in xenograft tumor sections derived from Hh-expressing colorectal cancer cell lines. To study the downstream genes regulated by Hh signaling, we treated a primary human colon myofibroblast, CCD-18Co, with SHH (1 ug/ml) or no treatment (control) in serum-free medium supplemented with 0.1% BSA for 72 hrs and performed microarray analysis (Affymetrix U133P) on these samples.

ORGANISM(S): Homo sapiens

PROVIDER: GSE29316 | GEO | 2011/05/17

SECONDARY ACCESSION(S): PRJNA138655

REPOSITORIES: GEO

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Expression data from colon fibroblasts treated with Sonic hedgehog homolog (SHH)

Project description:Canonical Hedgehog (Hh) signaling regulates the expression of genes that are critical to the patterning and development of a variety of organ systems. In adult, both ligand-dependent and ligand-independent Hh pathway activation are known to promote tumorigenesis. Recent studies have shown that in tumors promoted by Hh ligand, activation occurs within the stromal microenvironment (Yauch et al., 2009). In situ hybridization of the pathway target gene, Ptch1, shows that signaling is located at stromal perivascular fibroblast-like cells in xenograft tumor sections derived from Hh-expressing colorectal cancer cell lines. To study the downstream genes regulated by Hh signaling, we treated a primary human colon myofibroblast, CCD-18Co, with SHH (1 ug/ml) or no treatment (control) in serum-free medium supplemented with 0.1% BSA for 72 hrs and performed microarray analysis (Affymetrix U133P) on these samples. Three biological replicates of SHH stimulated and three replicates of unstimulated primary colon myofibroblast cells CCD-18Co were used in the experiment to analyze their gene expression.

2011-05-17 | E-GEOD-29316 | biostudies-arrayexpress

Gene expression in murine colon mucosa following activation of stromal Hedgehog signalling

2016-08-02 | GSE67172 | GEO

Gene expression in murine colon mucosa following activation of stromal Hedgehog signalling

Project description:In the intestine, Hedgehog (Hh) signalling orchestrates epithelial homeostasis in a bidirectional loop. Differentiated enterocytes secrete the ligand leading to active downstream signaling exclusively in the stroma. In turn, Hh-driven stromal factors contribute to the control of intestinal stem cell numbers and induce epithelial differentiation. To investigate the consequences of stromal Hh activation on the gene expression level, we performed microarray analysis on full-thickness colonic tissue from Col1a2CreER;Ptch1fl/fl mice (C57BL/6 background). Upon Cre-driven recombination, these mice lack the inhibiting Hh receptor Ptch1 specifically in Col1a2 expressing stroma cells, leading to stroma-specific activation of downstream Hh signaling. RNA was isolated from 1 cm of fresh-frozen whole colonic tissue from Col1a2CreER;Ptch1fl/fl mice (n = 4) and controls (n = 4) starting 1.5 cm from the anus 7 days after administration of 5mg Tamoxifen i.p. to activate Cre. RNA quality was assessed using the Agilent 2200 Tape Station system; RNA integrity numbers (RIN) >8 were considered sufficient. Affymetrix Mouse Gene ST 2.0 arrays were used. Robust multi-array average (RMA) median polish procedures were applied for normalization.

2016-08-02 | E-GEOD-67172 | biostudies-arrayexpress

Inhibition of Medulloblastoma growth by a sonic hedgehog (SHH) inhibitor

Project description:Aberrant activation of the Hedgehog (Hh) signaling pathway is implicated in the pathogenesis of many cancers, including medulloblastoma and basal cell carcinoma (BCC). In this study, using neonatally irradiated Ptch1+/- mice as a model of Hh-dependent tumors, we investigated the in vivo effects of MK-4101, a novel SMO antagonist, for treatment of medulloblastoma and BCC. Results clearly demonstrate a robust antitumor activity of MK-4101, achieved through the inhibition of proliferation and induction of extensive apoptosis in tumor cells. Of note, beside antitumor activity on transplanted tumors, MK-4101 was highly efficacious against primary medulloblastoma and BCC developing in the cerebellum and skin of Ptch1+/- mice. By identifying the changes induced by MK-4101 in gene expression profiles in tumors, we also elucidate the mechanism of action of this novel, orally administrable compound. MK-4101 targets the Hh pathway in the tumor cells, showing the maximum inhibitory effect on Gli1 activity. MK-4101 also induced deregulation of cell cycle and block of DNA replication in tumors. Members of the IGF and Wnt signaling pathways , were among the most highly deregulated genes by MK-4101, suggesting that the interplay among Hh, IGF and Wnt is crucial in Hh-dependent tumorigenesis. Altogether, the results of this preclinical study support a therapeutic opportunity for MK-4101 in the treatment of Hh-driven cancers, also providing useful information for combination therapy with drugs targeting pathways cooperating with Hh oncogenic activity. Gene expression data was generated (in replicates) from Medulloblastoma allografts collected at various time points and following low (40mpk) or high (80 mpk) or vehicle single dose (QD) or mutiple dose (BID) treatment with a SHH pathway inhibitor.

2016-03-14 | E-GEOD-77042 | biostudies-arrayexpress

Effects of Wnt3A on the transcriptome of CCD-18Co human colon fibroblasts

Project description:Purpouse: To compare the transriptome of CCD-18Co human colon fibroblasts treated with vehicle or Wnt3A. Methods: We treated triplicate plates of CCD-18Co cells with vehicle or Wnt3A during 24 h. Afterwards, we obtained total RNA and used it in RNA-seq experiments. Results: Our analysis rendered a total of 1136 differentially expressed genes (FDR<0.05), of which 662 were up-regulated and 474 were downregulated in response to Wnt3A. Conclusions: Wnt3A regulates a wide set of genes in CCD-18Co human colon fibroblasts

2017-10-30 | GSE89124 | GEO

Inhibition of Medulloblastoma growth by a sonic hedgehog (SHH) inhibitor

2016-03-14 | GSE77042 | GEO

Transcription profiling of mouse E18.5 intestinal mesenchyme treated with Sonic or Indian hedgehog ligand to identify targets regulated by Hedgehog signaling

Project description:Epithelial Hedgehog (Hh) ligands regulate several aspects of fetal intestinal organogenesis and emerging data implicate the Hh pathway in inflammatory signaling in adult colon. We investigated the effects of chronic Hh inhibition in vivo and profiled molecular pathways acutely modulated by Hh signaling in the intestinal mesenchyme. Experiment Overall Design: E18.5 intestinal mesenchyme was isolated and cultured. Mesenchyme was treated with Sonic (Shh) or Indian (Ihh) hedgehog ligand or Vehicle (control) acutely to identify targets regulated by Hh signaling in intestinal mesenchyme.

2009-11-10 | E-GEOD-17840 | biostudies-arrayexpress

Response to oxaliplatin in CCD-18Co

Project description:Response to oxaliplatin in CCD-18Co

| PRJNA750430 | ENA

DNA methylation profiling for CCD-18Co cells stably transfected with an artificial P16 DNA methyltransferase (P16-Dnmt)

Project description:Differential methylation between human normal fibroblast cell CCD-18Co transfected with P16-Dnmt or pTRIPZ control vector was identified using Illumina HumanMethylation 850K array. The genome-wide methylation detection experiment was carried out by CapitalBio Technology Company.

2022-12-31 | GSE111505 | GEO

Vitamin D and Wnt3A have additive and partially overlapping modulatory effects on gene expression and phenotype in human colon fibroblasts

Project description:The Wnt/b-catenin signalling pathway is essential for intestinal epithelium homeostasis, but its aberrant activation is a hallmark of colorectal cancer (CRC). Several studies indicate that the bioactive vitamin D metabolite 1a,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits proliferation and promotes epithelial differentiation of colon carcinoma cells in part through antagonism of the Wnt/b-catenin pathway. It is now accepted that stromal fibroblasts are crucial in healthy and pathologic intestine: pericryptal myofibroblasts are constituents of the stem cell niche and cancer-associated fibroblasts (CAFs) contribute to CRC progression. However, studies on the combined action of 1,25(OH)2D3 and Wnt factors in colon fibroblasts are lacking. Here we show by global transcriptomic studies that 1,25(OH)2D3 and Wnt3A have profound, additive, partially overlapping effects on the gene expression profile of CCD-18Co human colon myofibroblasts. Moreover, 1,25(OH)2D3 and Wnt3A inhibit CCD-18Co cell proliferation and migration, while 1,25(OH)2D3 reduces, but Wnt3A increases, their capacity to contract collagen gels (a marker of fibroblast activation). These data were largely confirmed in patient-derived primary colon normal fibroblasts and CAFs, and in fibroblasts from other origins. Our results indicate that 1,25(OH)2D3 and Wnt3A are strong regulators of colon fibroblast biology and contribute to a better knowledge of intestinal homeostasis and stromal fibroblast action in CRC.

2019-05-30 | GSE120106 | GEO

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