Transcriptional effects of co-culture on the spatiotemporal dynamics of T cell motility and cancer-T cell interactions [RNA-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE264477 | GEO | 2024/04/26
REPOSITORIES: GEO
Similar Datasets
Project description:Insufficient infiltration of cytotoxic T cells into solid tumors poses a major challenge in cancer immunotherapy, largely due to the intricate tumor microenvironment. To address this, we co-cultured mouse cancer cell lines (B16-WT or B16-OVA) with cancer-specific cytotoxic T cells (activated OT-1) in vitro to uncover the impact of cancer-T cell interactions on T cell motility, pivotal for effective tumor infiltration. To investigate the potential molecular mechanisms underlying T cell motility patterns in the two coculture contexts, we performed both bulk and single-cell RNA sequencing of cancer and T cells sorted from the co-culture systems at specific time points.
2024-04-26 | GSE264478 | GEO
Project description:In this study, combining 1) RNA-Sequencing on MCF-7 cell line, 2) a new computational approach to identify splice isoforms and 3) an extensive experimental validation (in vitro - on MCF-10, MCF-7 and MDA-MB-231 – and ex vivo – on human breast cancer tissues) we investigated simultaneously gene expression and alternative splicing in genes encoding for adhesion and motility-related molecules-, including Semaphorins and their receptors and co-receptors.
2015-06-01 | GSE68228 | GEO
Project description:Exogenous overexpression of the metastasis suppressor gene Nm23-H1 reduces the metastatic potential of multiple types of cancer cells. In addition, Nm23-H1 expression suppresses in vitro tumor cell motility and invasion, important correlates of metastasis. The molecular mechanism by which Nm23-H1 suppresses metastasis, motility and invasion has yet to be defined. However, mutational analysis of Nm23-H1 has revealed that substitution mutant P96S and S120G are unable to inhibit cell motility. To elucidate the molecular mechanism of Nm23-H1 motility suppression, we performed expression microarray analysis of an MDA-MB- 435 carcinoma cell line overexpressing wild-type Nm23-H1 and cross-compared the expression profile to lines expressing P96S and S120G mutants. Nine genes, MET, PTN, SMO, FZD1, L1CAM, MMP2, NETO2, CTGF and EDG2, were down regulated by wild-type but not by mutant Nm23-H1 expression (p<0.05). Reduced expression of these genes coincident with elevated Nm23-H1 expression was observed in human breast tumor cohorts, a panel of breast carcinoma cell lines and hepatocellular carcinomas from control and Nm23-M1 knockout mice. The functional significance of down regulated genes was assessed by transfection and in vitro motility assays. Only EDG2 overexpression significantly restored motility to Nm23-H1- suppressed cancer cells and it enhanced motility by 60-fold in these cells. In addition, silencing EDG2 expression with siRNA, reduced the motile phenotype of metastatic breast cancer cells. These data suggest that Nm23-H1 suppresses metastasis, at least in part, through downregulation of EDG2 expression and that compounds directed toward EDG2 may be useful for treating aggressive, low Nm23-H1-expressing breast tumors. Keywords: Human MDA-MB-435 Breast cancer derived cell lines
2007-04-30 | GSE7549 | GEO
Project description:Most cancer deaths are caused by metastases, which are the end-results of circulating tumor cells (CTC) that detach from the cancer primary and succeed to survive in distant organs. The aim of the present study was to develop a gene signature of CTC and to assess its prognostic relevance after surgery for pancreatic ductaladenocarcinoma (PDAC). A negative depletion fluorescence activated cell sorting (FACS) procedure was developed and validated with spiking experiments using cancer cell lines in whole human blood samples. This FACS-based method was used to enrich for CTC from the blood of 10 patients who underwent surgery for PDAC. Total RNA was isolated from 4 subgroup samples, i.e. CTC, haematological cells (G), original tumor (T), and non-tumoral pancreatic control tissue (P). After RNA quality control, samples of 6 patients were eligible for further analysis. Whole genome microarray analysis was performed after double linear amplification of RNA. The ‘Ingenuity Pathway Analysis’ software and AmiGO were used for functional data analyses. A CTC gene signature was developed and validated with the nCounter system on expression data of 78 primary PDAC using Cox regression analysis for disease-free (DFS) and overall survival (OS). Using stringent statistical analysis, we finally retained 8,152 genes to compare expression profiles of CTC vs. other subgroups, and found 1,059 genes to be differentially expressed. The pathway with the highest expression ratio in CTC was p38 mitogen-activated protein kinase (p38 MAPK) signaling, known to be involved in cancer cell migration. In the p38 MAPK pathway TGF-β1, cPLA2, and MAX were significantly upregulated. In addition, 9 other genes associated with both p38 MAPK signaling and cell motility were over-expressed in CTC. High co-expression of TGF-1 and our cell motility panel (≥ 4 out of 9 genes for DFS and ≥ 4 out of 9 genes for OS) in primary PDAC was identified as an independent predictor of DFS (p=0.041, HR (95% CI) = 1.885 (1.025 – 3.559)) and OS (p=0.047, HR (95% CI) = 1.366 (1.004 – 1.861)). Pancreatic CTC isolated from blood samples using a FACS-based negative depletion method,express a cell motility gene signature. The expression of this newly defined cell motility gene signature in the primary tumor is able to predict survival of patients who undergo surgical resection for pancreatic cancer. Total RNA was isolated from circulation tumor samples (CTC), haematological cells (G), original tumor (T), and non-tumor pancreatic control tissue (P) of patients with pancreatic ductal adenocarcinoma (PDAC). Gene expression profiles of CTC were compared to G, T, and P. The aim of the current study was to develop a ‘negative depletion strategy’ to isolate CTC without the exclusion of any particular subset of CTC, and to study their gene-expression profiles in order to find novel therapeutic targets and prognostic markers in patients with pancreatic cancer.
2012-12-18 | E-GEOD-18670 | biostudies-arrayexpress
Project description:Cell movement is an important character during epithelial-mesenchymal transition. A subpopulation with accelerated baseline motility (MG cells) or an immotile one (non-MG cells) from a colon cancer cell line (HCT116) were isolated. In this study, to investigate changes of global DNA methylation status between these two subpopulations, genomic DNA from these cells were subjected to DNA methylation array.
2018-12-26 | GSE114683 | GEO
Project description:Pseudomonas protegens Pf-5 motility TraDIS
| PRJEB56281 | ENA
Project description:Recent work has shown that cytotoxic T cells play a central role in immune-mediated control of cancers1-3, and monoclonal antibodies that target inhibitory receptors on T cells can induce significant clinical benefit in patients despite advanced disease4-6. However, many of the regulatory pathways that result in loss of T cell function within immunosuppressive tumors remain unknown. Here we show that such regulatory mechanisms can be systematically discovered in vivo in the tumor microenvironment. We devised a pool shRNA screening approach aimed at identifying genes that block the function of tumor-infiltrating CD8 T cells. We postulated that shRNAs targeting key inhibitors would enable robust T cell infiltration and proliferation in tumors, despite multiple inhibitory signals. Candidate shRNAs were discovered by transfer of shRNA-transduced T cells into tumor-bearing mice, followed by deep sequencing to quantify the representation of all hairpins in tumors and lymphoid organs. A subset of shRNAs induced T cell accumulation in tumors but not the spleen, demonstrating feasibility of discovering shRNAs with differential action across tissues. One of the targets was Ppp2r2d, a regulatory subunit of the family of PP2A phosphatases7. Control shRNA-transduced T cells underwent apoptosis upon recognition of melanoma cells, while Ppp2r2d shRNA-transduced T cells accumulated in tumors due to enhanced proliferation and reduced apoptosis. Ppp2r2d shRNAexpressing T cells also significantly delayed tumor growth. This in vivo approach has wide applications to dissect complex immune functions in relevant tissue microenvironments. OT-I derived T cells were transduced with shRNA's and adoptively transferred to B16 tumor bearing mice. Following incubation the T cells were purified from either tumors or spleens. The shRNA's targeted either a control gene (LacZ) or one of 5 selected genes found to regulate the presence of T cells in tumors vs in spleen
2014-03-14 | E-GEOD-53388 | biostudies-arrayexpress
Project description:Swarming motility in Pseudomonas aeruginosa
| PRJNA497479 | ENA
Project description:Swarming motility induces multidrug resistance
| PRJNA566190 | ENA
Project description:High-grade serous carcinoma (HGSC) is the most aggressive and predominant form of epithelial ovarian cancer and the leading cause of gynecological cancer death. We have previously shown that CTCFL (also known as BORIS, Brother of the Regulator of Imprinted Sites) is expressed in a large proportion of ovarian cancers, which is associated with global and promoter-specific DNA hypomethylation, advanced tumor stage, and poor prognosis. To explore its functional role in HGSC, we expressed BORIS in human fallopian tube secretory epithelial cells (FTSEC), the presumptive cell of origin for HGSC. BORIS-expressing cells exhibited increased motility and invasion, and BORIS expression was associated with alterations in several cancer-associated gene expression networks, including fatty acid metabolism, TNF signaling, cell migration, and ECM-receptor interactions. Importantly, GALNT14, a glycosyltransferase gene previously implicated in cancer cell migration and invasion, was highly induced by BORIS, and GALNT14 knockdown significantly abrogated BORIS-induced cell motility and invasion. In addition, in silico analyses provided evidence for BORIS and GALNT14 co-expression in several human cancers. Finally, ChIP-seq demonstrated that expression of BORIS in FTSEC cells was associated with de novo and enhanced binding of CTCF at hundreds of loci, many of which correlated with activation of transcription at target genes, including GALNT14. Taken together, our data indicate that BORIS may promote cell motility and invasion in HGSC via upregulation of GALNT14, and suggests BORIS as a potential therapeutic target in this malignancy.
2019-07-01 | GSE131931 | GEO