Activation of β-adrenoceptor signaling inhibits extracellular matrix deposition of human bladder smooth muscle cells
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE128618 | GEO | 2022/03/20
REPOSITORIES: GEO
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Project description:Activation of β-adrenoceptor signaling inhibits extracellular matrix deposition of human bladder smooth muscle cells
| PRJNA528287 | ENA
Project description:We assessed the pivotal effect of YAP on the proliferation of human bladder smooth muscle cells (hBdSMCs) under different ECM stiffnesses. We investigated the interaction between YAP and Smad3 through mass spectrometry and immunoprecipitation (IP). Transcriptome sequencing was used to predict the phenotype and signalling pathways. CUT and TAG sequencing was utilized to analyse the target genes of Smad3, and a dual-luciferase reporter assay was used to confirm the sequencing results. The YAP inhibitor CA3 was used in a partial bladder outlet obstruction (pBOO) rat model construction to evaluate bladder smooth muscle proliferation in vivo.
2022-04-13 | PXD033188 |
Project description:A major problem in cancer research is the lack of a tractable model for delayed metastasis. Herein we show that cancer cells suppressed by SISgel, a gel-forming normal ECM material derived from Small Intestine Submucosa, in flank xenografts show properties of suppression and re-activation that are very similar to normal delayed metastasis and suggest they can serve as a novel model for developing therapeutics to target micrometastases or suppressed cancer cells. Co-injection with SISgel suppressed the malignant phenotype of highly invasive J82 and T24 bladder cancer cells and highly metastatic JB-V cells in flank xenografts. Cells could remain viable up to 120 days without forming tumors and appeared much more highly differentiated and less atypical than tumors from cells co-injected with Matrigel. In 40% of SISgel xenografts, growth resumed in the malignant phenotype after a period of suppression or dormancy for at least 30 days and was more likely with implantation of 3 million cells or more cells. Ordinary Type I collagen did not suppress malignant growth, and tumors developed about as well with collagen as with Matrigel. A clear signal in gene expression over different cell lines was not seen, but in contrast, Reverse Phase Protein Analysis of 250 proteins across 4 cell lines identified a clear signal at the protein level involving Integrin Linked Kinase (ILK) signaling that was confirmed by an ILK inhibitor. We suggest that cancer cells suppressed on SISgel could serve as a model for dormancy and re-awakening to develop therapeutic targets for micrometastases. Earlier we demonstrated that the phenotype of bladder cancer cells was radically different in 3-dimensional organotypic culture when grown on a normal extracellular matrix preparation (SISgel) as compared to that observed on a cancer-modulated permissive extracellular matrix preparation (Matrigel). SISgel is a gel-forming material derived from acellular small intestine submucosa, whereas Matrigel is a basement membrane preparation obtained from a mouse sarcoma. On Matrigel the bladder cancer cells recapitulated the phenotype reported for the original tumor; in sharp contrast, most of the malignant properties were lost when the cells were grown on SISgel. Cell lines derived from papillomas formed a layered structure reminiscent of normal urothelium, whereas cell lines derived from higher grade tumors formed a noninvasive layer of cells. These findings suggested that growth of cancer cells on normal ECM could provide a model to investigate the phenomenon of suppression of malignancy by normal ECM in metastasis and recurrence. In this study we explored whether the phenotypic suppression seen in organotypic culture of bladder cancer cells on SISgel also is observed in vivo. Positive findings support the use of SISgel as a model for investigations of the dormant or suppressed tumor cell phenotype and of mechanisms by which the normal ECM exerts an inhibitory influence on tumorigenesis and metastasis. The findings strongly suggest that interactions of cancer cells with normal ECM play an important role in recurrence and metastasis and further suggest that targeting suppressed cells could represent a heretofore unexploited point of vulnerability in cancer therapy.
2014-02-20 | E-GEOD-35947 | biostudies-arrayexpress
Project description:This study was undertaken to identify how gene expression of the RT4 bladder papilloma cells respond to extracellular matrics (ECM) Matrigel. Gene expression profile of RT4 cells grown on Plastic was compared with expression profiles of RT4 cells grown on Matriges over 12 hours-9 days timecourse. Total 5881 hypervariable (HV) genes were found to vary significantly over the time points, indicating a response to matrix change. Correlational clustering showed these HV genes fell into distinct families, predominantly genes which became highly expressed on ECM. Another cluster show genes expressed at 12 hours after grown on Matrigel and third cluster show genes whose expression decreased below noise level on Matrigel. This indicate that processes responsible for cell adaptation to ECM happen within first 12 hours and the second cluster form last response of those active processes. Over 1-9 days of cell grows on Matrigel those genes are constantly expressed. Cell signaling and cellular growth and proliferation accounted for major functions for those genes. G-protein signaling, immune response and NF-kB signaling accounted for most dramatically affected canonical pathways. Genes sharing similar ontologies also share several overrepresented transcription regulatory elements confirmed by independent experiment on Panomics platform.Thus, rapid response for ECM orchestrated by several transcription factors was observed. Identified canonical pathways indicate possible targets for manipulating cell phenotype on ECM. Keywords: extracellular matrix, gene expression, RT4, Matrigel, microarray, time course
2008-06-10 | GSE9291 | GEO
Project description:This study was undertaken to identify how gene expression of the RT4 bladder papilloma cells respond to extracellular matrics (ECM) Matrigel. Gene expression profile of RT4 cells grown on Plastic was compared with expression profiles of RT4 cells grown on Matriges over 12 hours-9 days timecourse. Total 5881 hypervariable (HV) genes were found to vary significantly over the time points, indicating a response to matrix change. Correlational clustering showed these HV genes fell into distinct families, predominantly genes which became highly expressed on ECM. Another cluster show genes expressed at 12 hours after grown on Matrigel and third cluster show genes whose expression decreased below noise level on Matrigel. This indicate that processes responsible for cell adaptation to ECM happen within first 12 hours and the second cluster form last response of those active processes. Over 1-9 days of cell grows on Matrigel those genes are constantly expressed. Cell signaling and cellular growth and proliferation accounted for major functions for those genes. G-protein signaling, immune response and NF-kB signaling accounted for most dramatically affected canonical pathways. Genes sharing similar ontologies also share several overrepresented transcription regulatory elements confirmed by independent experiment on Panomics platform.Thus, rapid response for ECM orchestrated by several transcription factors was observed. Identified canonical pathways indicate possible targets for manipulating cell phenotype on ECM. Keywords: extracellular matrix, gene expression, RT4, Matrigel, microarray, time course Three dimensional gel cultures with Matrigel were performed by layering 0.8 mls of ice cold Matrigel onto polyethylene terephthalate membranes of 6-well cell culture inserts (Falcon, Becton-Dickinson Labware, Franklin Lakes, NJ). Gels were solidified at 37º C. RT4 cells were trypsinized, brought up on 20 mls McCoys media with 10% Fetal Calf Serum (FCS). Cells were centrifuged then brought up in McCoys media with 10% FCS to a concentration of 500,000 cells/250µl. 250µl added on top of each solidified matrigel disc and 2mls of McCoys with 10% FCS layered underneath each culture insert. Cells were maintained for 10 days and media replenished underneath the insert twice a week. Cells were harvested at 12 hrs, 24hrs, 2 days, 3 days, 4days, 6 days, 7 days, 8 days, and 9 days of growth in culture using Matrisperse (Falcon, Becton-Dickinson Labware, Franklin Lakes, NJ) and RNA collected. Data were normalized as was described previously in Dozmorov I et al., Nucleic Acids Res. 2004 Oct 28;32(19). In general, intensities were converted to expression and normalized to low-expressed genes, which provide possible technical noise level. The arrays are then adjusted to each other by robust linear regression and this Log10 transformed data presented for each sample. Group of low-expressed genes is selected by normal distribution fitting. This group provides internal standard of measurement noise (ISMN). Genes above 5SD from mean of ISMN were selected as expressed
2010-05-26 | E-GEOD-9291 | biostudies-arrayexpress
Project description:corosolic acid inhibiting bladder cancer via targeting cell cycle and inducing mitophagy
2021-06-24 | PXD026919 |
Project description:Growing evidence has indicated that miR-193 is involved in the initiation and progression of malignancy, such as bladder cancer, hepatocellular carcinoma, renal cell carcinoma, and colorectal cancer. Nevertheless, the mechanisms of miR-193 in the development of metastatic bladder cancer remains unknown. In the current study, we clarified the association of miR-193/N-myc was implicated in cancer metastasis. miR-193 expression increased in metastatic bladder cancer biopsies compared to the primary cases. Moreover, the elevation of miR-193 was correlated with the invasiveness, lymph node metastasis, and advanced stages of bladder cancer significantly. Downregulation of miR-193 by shRNA hampered proliferation and migration while inducing cell apoptosis. Furthermore, miR-193 sponged N-myc and diminished miR-103 expression. Overexpression of miR-193 released oncogene N-myc expression, leading to the promotion of cell proliferation and migration. Besides, knockout of miR-193 suppressed tumor growth in the human T24 mice models. Briefly, the present findings suggested that miR-193-N-myc were novel promising pathways for conquering bladder cancer progression.
2021-01-13 | GSE164682 | GEO
Project description:Ten-Eleven Translocation 1 (TET1) is a member of methylcytosine dioxygenase, which catalyse 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) that promote the demethylation process. The diminished expression of TET1 protein and 5-hmC in many tumors indicate a critical role for the maintenance of cell stability. However, role of TET1 in bladder cancer development remains unclear. Here we found that TET1 expression was downregulated in bladder cancer tissues compared with normal urothelium and was inversely related to patient overall survival. TET1 silencing in bladder cancer cells increase proliferation and inhibited cell migration and invasion while its re-expression inhibits their proliferation and the growth of tumor xenografts. Furthermore, we found that TET1 binds to the promoter of the TSG to maintain its hypomethylated which interacts with β-catenin and suppress its nuclear translocation, thus inhibiting β-catenin transcriptional activity and downstream genes. In conclusion, TET1 acts as a tumor suppressor gene in bladder cancer cells by suppressing β-catenin signaling. This study may facilitate efforts to therapeutic strategy for patients with bladder cancer.
2020-06-16 | GSE137646 | GEO
Project description:Urothelial carcinoma (UC) is the most common histologic subtype of bladder cancer. The administration of mitomycin C (MMC) into bladder after transurethral resection of the bladder tumor (TURBT) is a common treatment strategy for preventing recurrence after surgery. We previously applied hydrostatic pressure combined with MMC in UC cells and found that hydrostatic pressure synergistically enhanced MMC-induced UC cell apoptosis via the Fas/FasL pathways. To understand the alteration of gene expressions in UC cells caused by hydrostatic pressure and MMC, oligonucleotide microarray was used to explore all of the differentially expressed genes. After bioinformatics analysis and gene annotation, Toll-like receptor 6 (TLR6) and connective tissue growth factor (CTGF) showed significant up-regulation among altered genes, and their expressions with each treatment of UC cells were validated by quantitative real-time PCR (qPCR). We conclude that under treatment with MMC and hydrostatic pressure, UC cells showed increasing apoptosis via extrinsic pathways through upregulation of TLR6 and CTGF.
2016-03-21 | GSE45385 | GEO
Project description:Smooth muscle cells (SMCs) are important in a number of physiological systems and organs, including the cardiovascular system. The hallmark property of differentiated SMCs is the ability to contract, but contractile SMCs themselves show a range of phenotypes allowing prolonged tonic contraction in vascular smooth muscle or rapid phasic contraction in tissues such as bladder. Another distinctive characteristic, in contrast with terminally differentiated striated muscle cells, is that SMCs exhibit phenotypic plasticity. Vascular SMCs are able to modulate their phenotype along a continuum between a contractile phenotype, characteristic of healthy blood vessels, and a more proliferative âsyntheticâ phenotype, so-named for the enhanced synthesis and secretion of extracellular matrix components. Synthetic phenotype cells are found in a number of pathological situations such as atherosclerosis and arterial injury. We used mouse exon-junction (MJAY) arrays to gain insights into both the global contribution of alternative splicing events in re-shaping the transcriptome of dedifferentiating mouse aorta and bladder SMCs, and into the underlying regulatory mechanisms of the alternative splicing program. Affymetrix splice junction arrays (MJAY) were used to profile changes in both alternative splicing and transcript levels during the phenotypic modulation of smooth muscle cells when placed in culture. RNA extracted from intact aorta and bladder smooth muscle tissue was used for differentiated samples. For dedifferentiated, proliferative samples smooth muscle cells were enzymatically dispersed and grown in tissue culture for a week. Triplicate RNA samples were prepared from smooth muscle tissue of mouse aorta and bladder (differentiated) and from smooth muscle cells from each tissue cultured for 7 days (proliferative). The samples allowed comparison of alternative splicing (and other transcriptome) changes between differentiated and proliferative smooth muscle cell samples from two distinct types of smooth muscle cell, as well as allowing direct comparison of aorta (tonic smooth muscle) and bladder (phasic smooth muscle).
2016-07-01 | E-MTAB-4841 | biostudies-arrayexpress