MicroRNA expression in prostate cancer cells stimulated with cancer associated fibroblasts
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Paolo Gandellini
PROVIDER: E-GEOD-42699 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Tumor microenvironment is a strong determinant for the acquisition of metastatic potential of cancer cells. It has been demonstrated (Giannoni E et al., Cancer Res 2010) that cancer associated fibroblasts (CAF) elicit an epithelial-mesenchymal transition (EMT) in prostate cancer (PCa) cells, leading to enhanced tumor cell aggressiveness. Here, we investigated the involvement of microRNAs (miRNA) in such malignant tumor-stroma interplay, to identify possible tools to counteract metastasis dissemination.
2013-09-01 | GSE42699 | GEO
Project description:Epithelial-to-mesenchymal transition (EMT) and cancer stem cells play relevant roles in metastasis and drug resistance in castration-resistant PCa. Conditioned-media from Cancer-Associated Fibroblasts from two patients with aggressive PCa induce EMT, reversible DNA methylation and transcriptional variations in androgen independent PC3, but not in androgen dependent LN-CaP cells. Focal CpG islands hyper-methylation associated to transcriptional repression of epithelial markers occurs together with widespread hypo-methylation, including promoters of EMT and stemness regulating genes resulting in their transcriptional activation. Remarkably, DNA methylation and transcription patterns are entirely reverted upon exposure to serum-free medium (mesenchymal-to-epithelial transition). DNMT3A is required for de novo methylation and silencing of CDH1 and GRHL2, the ZEB1 direct repressor, while its knock-down prevents EMT entry. These unprecedented results highlight that CAF-released factors induce reversible DNA methylation patterns required for transcriptional variations essential for EMT and stemness in androgen independent PCa cells, suggesting that similar plasticity might occur in tumour microenvironment.
2017-03-09 | E-MTAB-4752 | biostudies-arrayexpress
Project description:Epithelial-to-mesenchymal transition (EMT) and cancer stem cells play relevant roles in metastasis and drug resistance in castration-resistant prostate cancer (PCa). Conditioned-media from Cancer-Associated Fibroblasts from two patients with aggressive PCa induce EMT, reversible DNA methylation and transcriptional variations in androgen independent PC3, but not in androgen dependent LN-CaP cells. Focal CpG islands hyper-methylation associated to transcriptional repression of epithelial markers occurs together with widespread hypo-methylation, including promoters of EMT and stemness regulating genes resulting in their transcriptional activation. Remarkably, DNA methylation and transcription patterns are entirely reverted upon exposure to serum-free medium (mesenchymal-to-epithelial transition). DNMT3A is required for de novo methylation and silencing of CDH1 and GRHL2, the ZEB1 direct repressor, while its knock-down prevents EMT entry. These unprecedented results highlight that CAF-released factors induce reversible DNA methylation patterns required for transcriptional variations essential for EMT and stemness in androgen independent PCa cells, suggesting that similar plasticity might occur in tumour microenvironment. This submission contains data and metadata from the methylation profiling by array of PC-3 cells treated with conditioned media from Human prostate fibroblasts (HPFs) and cancer associated fibroblasts (CAFs).
2017-03-03 | E-MTAB-4753 | biostudies-arrayexpress
Project description:Investigation of whole genome gene expression level changes in response to tunicamycin, an inhibitor of protein N-glycosylation, in Candida glabrata CBS138 delta-cnb1, delta-crz1, delta-slt2, and delta-ire1 mutants, compared to the wild-type strain. The mutations engineered into these strains render them hypersusceptible to tunicamycin. The mutants analyzed in this study are further described in Miyazaki, T. et al. (2010) Antimicrob Agents Chemother. 54(4):1639-1643 (PMID: 20100876) and Miyazaki, T. et al. (2010) FEMS Yeast Res 10(3):343-352, 2010 (PMID: 20214686).
2013-05-31 | GSE29855 | GEO
Project description:Affymetrix expression profiling was used to evaluate the association between IL13Rα2 expression, and mesenchymal, proneural, classical and neural signature genes expression for glioma subclasses defined by Verhaak et al (Cancer Cell; 2010).
2014-01-29 | GSE40904 | GEO
Project description:In order to metastasize, few cells need to detach from the primary tumor, and transition through the circulation to distant sites to establish new solid tumor metastases. The gene expression changes occurring between these transitions are poorly understood, and controversial findings have been reported regarding transitions between epithelial (E) and mesenchymal (M) cell states. To model the metastasis process in vitro, here we examined the dynamics of gene expression changes and respective cell fates that are occurring in cells that are transitioning from adhesion culture to suspension 3D culture (mammospheres) and back to adhesion culture in vitro. We found that mammosphere and replating cultures of epithelial (E) cell lines (HP cells and E clones) led to enrichment for mesenchymal (M) signatures characteristic of the mesenchymal cell lines, indicative of an epithelial to mesenchymal transition (EMT), but retainment of E-specific signatures (Grosse-Wilde et al., 2015). This co-expression of E and M signatures was stably maintained between the mammosphere state in suspension and in replated cells, indicating a stable E/M gene expression state by partial EMT in E cell lines, which has been associated with a stem-like state (Grosse-Wilde et al., 2015; Jolly et al., 2014; Lu et al., 2014; Zhang et al., 2014). Interestingly, mammosphere suspension culture of mesenchymal M clones also resulted in co-expression of E and M signatures generated by partial mesenchymal to epithelial transition (MET). However, in stark contrast to E clones and HP cells, immediately upon replating M cell-derived mammospheres to adhesion lost the intermediate E/M state and converted back to stable expression of M signatures indicative of rapid EMT. This suggests that the intermediate state in M cells is very unstable. Together, these replating data suggest that prolonged detachment of epithelial-derived cells leads to loss of expression of E signatures and EMT. Life-threatening macrometastases typically recapitulate the gene expression of the primary tumor, which requires expression of E signatures, while the mesenchymal micrometastases are frequent but not-proliferative and harmless. Since all HMLER cell lines independent of their initial E or M state converged to an M state upon expansion in suspension, our data suggest that induction of EMT in suspended HMLER cells may be one reason for the observed benign non-metastatic character of HMLER cells when used in mouse xenograft experiments, and for their metastatic inefficiency. Our datasets of the replating kinetic may be useful to identify which pathways are involved in the processes enabling the mixed HP population to maintain a stable E/M expression signature and a more stem-like state, which we have identified as caused by cell-cell cooperation between phenotypically different E and M cell-types. By contrast, M cells can only transiently assume this E/M gene expression state, and not generate a stable phenotypic heterogeneity and therefore absence of cooperation between E and M cell-types. Instability of the intermediate stem-like E/M state in M cell-types and rapid conversion to the M state can explain why 1) pure M populations are often phenotypically stable and are not undergoing MET in vitro (Schmidt et al., 2015; Zhang et al., 2014), 2) why pure M populations are less aggressive resulting in less metastases than mixed cooperating E and M cell populations (Ocaña et al., 2012; Tsuji et al., 2008) or 3) why complete EMT results in more benign less metastasizing tumors than incomplete EMT (Tran et al., 2014; Tsai et al., 2012) and finally 4) why expression of M traits in primary tumors are associated with good patient outcomes and less metastases than E signatures (Kim et al., 2011; Mylona et al., 2008; Tan et al., 2014). Dontu, G., Abdallah, W.M., Foley, J.M., Jackson, K.W., Clarke, M.F., Kawamura, M.J., and Wicha, M.S. (2003). In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev. 17, 1253–1270. Elenbaas, B., Spirio, L., Koerner, F., Fleming, M.D., Zimonjic, D.B., Donaher, J.L., Popescu, N.C., Hahn, W.C., and Weinberg, R.A. (2001). Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells. Genes Dev 15, 50–65. Grosse-Wilde, A., Fouquier d’Hérouël, A., McIntosh, E., Ertaylan, G., Skupin, A., Kuestner, R.E., del Sol, A., Walters, K.-A., and Huang, S. (2015). Stemness of the hybrid Epithelial/Mesenchymal State in Breast Cancer and Its Association with Poor Survival. PLOS ONE 10, e0126522. Jolly, M.K., Huang, B., Lu, M., Mani, S.A., Levine, H., and Ben-Jacob, E. (2014). Towards elucidating the connection between epithelial-mesenchymal transitions and stemness. J. R. Soc. Interface R. Soc. 11, 20140962. Kim, H.J., Kim, M.-J., Ahn, S.H., Son, B.H., Kim, S.B., Ahn, J.H., Noh, W.C., and Gong, G. (2011). Different prognostic significance of CD24 and CD44 expression in breast cancer according to hormone receptor status. The Breast 20, 78–85. Lu, M., Jolly, M.K., Onuchic, J., and Ben-Jacob, E. (2014). Toward decoding the principles of cancer metastasis circuits. Cancer Res. 74, 4574–4587. Mylona, E., Giannopoulou, I., Fasomytakis, E., Nomikos, A., Magkou, C., Bakarakos, P., and Nakopoulou, L. (2008). The clinicopathologic and prognostic significance of CD44+/CD24−/low and CD44−/CD24+ tumor cells in invasive breast carcinomas. Hum. Pathol. 39, 1096–1102. Ocaña, O.H., Córcoles, R., Fabra, Á., Moreno-Bueno, G., Acloque, H., Vega, S., Barrallo-Gimeno, A., Cano, A., and Nieto, M.A. (2012). Metastatic Colonization Requires the Repression of the Epithelial-Mesenchymal Transition Inducer Prrx1. Cancer Cell 22, 709–724. Schmidt, J.M., Panzilius, E., Bartsch, H.S., Irmler, M., Beckers, J., Kari, V., Linnemann, J.R., Dragoi, D., Hirschi, B., Kloos, U.J., et al. (2015). Stem-Cell-like Properties and Epithelial Plasticity Arise as Stable Traits after Transient Twist1 Activation. Cell Rep. 10, 131–139. Tan, T.Z., Miow, Q.H., Miki, Y., Noda, T., Mori, S., Huang, R.Y.-J., and Thiery, J.P. (2014). Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients. EMBO Mol. Med. 6, 1279–1293. Tran, H.D., Luitel, K., Kim, M., Zhang, K., Longmore, G.D., and Tran, D.D. (2014). Transient SNAIL1 Expression Is Necessary for Metastatic Competence in Breast Cancer. Cancer Res. 74, 6330–6340. Tsai, J.H., Donaher, J.L., Murphy, D.A., Chau, S., and Yang, J. (2012). Spatiotemporal Regulation of Epithelial-Mesenchymal Transition Is Essential for Squamous Cell Carcinoma Metastasis. Cancer Cell 22, 725–736. Tsuji, T., Ibaragi, S., Shima, K., Hu, M.G., Katsurano, M., Sasaki, A., and Hu, G. -f. (2008). Epithelial-Mesenchymal Transition Induced by Growth Suppressor p12CDK2-AP1 Promotes Tumor Cell Local Invasion but Suppresses Distant Colony Growth. Cancer Res. 68, 10377–10386. Zhang, J., Tian, X.-J., Zhang, H., Teng, Y., Li, R., Bai, F., Elankumaran, S., and Xing, J. (2014). TGF- -induced epithelial-to-mesenchymal transition proceeds through stepwise activation of multiple feedback loops. Sci. Signal. 7, ra91–ra91.
2015-07-10 | GSE70279 | GEO
Project description:To identify hypermethylated genes in induced pluripotent stem cell lines, human embryonic stem cell lines, and non-nucleofected CD34+ CB cells, indicated cell lines were treated with 5-aza-2′-deoxycytidine (DAC) or trichostatin A (TSA), and drug-induced changes in gene expression vs control treatment (PBS) were identified using Agilent two-color arrays, using the experimental methods of Ohm et al. (Cancer Res 70:7662-7673 2010).
2017-12-31 | GSE44941 | GEO
Project description:Introduction: Ampullary cancer is a relatively rare entity and usually treated by pancreatoduodenectomy followed by adjuvant therapy. The intestinal subtype is associated with markedly improved prognosis after resection. Only few cell lines are available for in vitro studies of ampullary cancer and they have not been collectively characterized. Methods: We characterized available ampullary cancer cell lines by subtype maker expression, epithelial-mesenchymal transition (EMT) features, growth and invasion, drug sensitivity and response to cancer-associated fibroblast conditioned medium (CAF-CM). Results: On the basis of EMT features, subtype marker expression, growth, invasion and drug sensitivity three types of cell lines could be distinguished: mesenchymal-like, pancreatobiliary-like and intestinal-like. In response to CAF-CM, enhanced growth, EMT induction as well as suppression of intestinal differentiation markers were observed, but in a heterogenous pattern. Also proteomic analysis of the CAF response distinguished intestinal-like from other cell lines. Discussion: Most of the available AMPAC cell lines seem to reflect a poorly differentiated pancreatobiliary or mesenchymal-like phenotype, consistent with their origin. We suggest that the best cell line model for intestinal-like AMPAC is the SNU869 cell line, while others seem to reflect aggressive AMPAC subtypes.
2017-03-29 | MSV000080802 | MassIVE
Project description:Introduction: Ampullary cancer is a relatively rare entity and usually treated by pancreatoduodenectomy followed by adjuvant therapy. The intestinal subtype is associated with markedly improved prognosis after resection. Only few cell lines are available for in vitro studies of ampullary cancer and they have not been collectively characterized. Methods: We characterized available ampullary cancer cell lines by subtype maker expression, epithelial-mesenchymal transition (EMT) features, growth and invasion, drug sensitivity and response to cancer-associated fibroblast conditioned medium (CAF-CM). Results: On the basis of EMT features, subtype marker expression, growth, invasion and drug sensitivity three types of cell lines could be distinguished: mesenchymal-like, pancreatobiliary-like and intestinal-like. In response to CAF-CM, enhanced growth, EMT induction as well as suppression of intestinal differentiation markers were observed, but in a heterogenous pattern. Also proteomic analysis of the CAF response distinguished intestinal-like from other cell lines. Discussion: Most of the available AMPAC cell lines seem to reflect a poorly differentiated pancreatobiliary or mesenchymal-like phenotype, consistent with their origin. We suggest that the best cell line model for intestinal-like AMPAC is the SNU869 cell line, while others seem to reflect aggressive AMPAC subtypes.
2016-03-14 | PXD002657 | Pride
Project description:Epithelial-to-Mesenchymal Transition (EMT) is involved in prostate cancer metastatic progression and its plasticity suggests epigenetic implications. Deregulation of UHRF1/DNMT1, DNMT3A and miRNAs play a role in EMT, but their interplay has not been clarified yet. Here, we identify miR-720 and miR-1260a as new DNMT3A regulators through miRNA microarray performed on UHRF1 silenced Androgen Receptor (AR) non-responsive (PC3) cell extracts, and subsequent target validation and functional overexpression and downregulation in PC3 and AR responsive LNCaP cells, respectively. These miRNAs inversely correlated with DNMT3A in our ex-vivo model of EMT in PC3 but not in LNCaP cells, induced with conditioned media from patient-derived Cancer-Associated Fibroblasts (CM-CAF). miR-720 and miR-1260a were expressed in very few patients from the PRAD TCGA data set expressing an EMT or MET (Mesenchymal-to-Epitelial Transition) signature; miR-200 family (miR-200a/b, -141, -429), along with miR-205 and miR-203, were downregulated in EMT patients as they modulate key EMT factors. These latter miRNAs resulted hyper-methylated at their promoters in our ex-vivo EMT prostate cancer model, while in the EMT PRAD TCGA data set only miR200c and miR141 promoters displayed a diffused hyper-methylated pattern inversely correlated with their transcriptional expression. Chromatin immunoprecipitation experiments performed on CM-CAF induced PC3 cells extracts showed that DNMT3A gets recruited onto the promoters of the latter two miRNAs, coupled with a marked increase of H3K27me3 and H3K9me3 and/or the decrease of H3K4me3 and H3K36me3. Altogether, our results point to a DNMT3A regulatory role of key miRNAs for EMT in prostate cancer.
2021-11-20 | E-MTAB-9835 | biostudies-arrayexpress