Friend or Foe? Primary Tumor represses distant metastases' growth via exosomal miRNA-1
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA883386 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Recently, exosome has been treated as a key mechanism for cell-to-cell communication. We thus demonstrated the roles of exosomes for the encoding messages between primary tumors and metastases. To investigate the difference between pTDE miRNA (primary tumor-derived exosomal miRNA) and mDE miRNA (metastases-derived exosomal miRNA), we isolated exosomal miRNA from each cell lines. Next, we performed small RNA sequencing for miRNA profiling. Compared with pTDE and mDE miRNAs, miR-1 is specifically abundunt in pTDE and also shows therapeutic effects to repress the growth of metastases after primary tumor resection.
2024-01-01 | GSE213969 | GEO
Project description:Results When compared with each other, primary tumors and regional metastases showed statistically indistinguishable gene expression patterns. Supervised analyses comparing patients with distant metastases versus primary tumors or regional metastases showed that the distant metastases were distinct and distinguished by the lack of expression of fibroblast/mesenchymal genes, and by the high expression of a 13-gene profile (that is, the âvascular endothelial growth factor (VEGF) profileâ) that included VEGF, ANGPTL4, ADM and the monocarboxylic acid transporter SLC16A3. At least 8 out of 13 of these genes contained HIF1α binding sites, many are known to be HIF1α-regulated, and expression of the VEGF profile correlated with HIF1α IHC positivity. The VEGF profile also showed prognostic significance on tests of sets of patients with breast and lung cancer and glioblastomas, and was an independent predictor of outcomes in primary breast cancers when tested in models that contained other prognostic gene expression profiles and clinical variables. Conclusions These data identify a compact in vivo hypoxia signature that tends to be present in distant metastasis samples, and which portends a poor outcome in multiple tumor types. Microarrays and immunohistochemistry were used to analyze primary breast tumors, regional (lymph node) metastases, and distant metastases in order to identify biological features associated with distant metastases.
2009-03-31 | E-GEOD-3521 | biostudies-arrayexpress
Project description:With the intent of identify alterations associated with the development of distant metastases in Papillary Thyroid Cancer (PTCs), we design a case-control study and performed genome-wide copy number variation analysis by Affymetrix Oncoscan FFPE Kit on 34 PTCs that developed distant metastases (DM-PTCs), 61 PTCs without distant metastases (CTRL-PTCs), and on 7 tissue from distant metastatic site
2018-03-01 | E-MTAB-5194 | biostudies-arrayexpress
Project description:Results When compared with each other, primary tumors and regional metastases showed statistically indistinguishable gene expression patterns. Supervised analyses comparing patients with distant metastases versus primary tumors or regional metastases showed that the distant metastases were distinct and distinguished by the lack of expression of fibroblast/mesenchymal genes, and by the high expression of a 13-gene profile (that is, the ‘vascular endothelial growth factor (VEGF) profile’) that included VEGF, ANGPTL4, ADM and the monocarboxylic acid transporter SLC16A3. At least 8 out of 13 of these genes contained HIF1α binding sites, many are known to be HIF1α-regulated, and expression of the VEGF profile correlated with HIF1α IHC positivity. The VEGF profile also showed prognostic significance on tests of sets of patients with breast and lung cancer and glioblastomas, and was an independent predictor of outcomes in primary breast cancers when tested in models that contained other prognostic gene expression profiles and clinical variables. Conclusions These data identify a compact in vivo hypoxia signature that tends to be present in distant metastasis samples, and which portends a poor outcome in multiple tumor types.
2009-03-31 | GSE3521 | GEO
Project description:Metastases originate from primary tumors and reach distant organs. Growing evidence suggests that metastases are under the control of primary tumors even outside the primary site; however, the mechanisms by which primary tumors remotely control metastases remain unclear. Here, we discovered a molecular mechanism by which primary tumors suppress metastatic growth. Interestingly, we found that extracellular vesicles (EVs) derived from the primary tumor can inhibit the growth of metastases both in vitro and in vivo. miR-1 was particularly enriched in primary tumor-derived EVs (pTDEs) and was found to be responsible for the suppression of metastatic growth. Mechanistically, intracellular reactive oxygen species (ROS) production and DNA damage were induced, which led to cell cycle arrest. Collectively, our data demonstrate that primary tumors restrict the growth of distant metastases via miR-1 in pTDEs and that miR-1 could potentially be used as an antimetastatic agent.
| S-EPMC10985072 | biostudies-literature
Project description:We present a novel approach for investigating transcriptomic differences between primary colorectal cancers (CRC) and distant CRC metastases, which may help to identify primaries at high risk for future dissemination and to inform the development of metastasis-targeted therapies. Eliminating tissue specificity of the “host” organs where tumors are located and adjusting for confounders such as exposure to chemotherapy and radiation, allows for an effective comparison of primary CRC and metastatic lesion transcriptomes at both the gene and pathway levels. Using this approach, our discovery-validation design identified that metastases are characterized by reduced epithelial-mesenchymal-transition (EMT) but increased MYC target and DNA repair pathway activities. The most significant gene-level expression differences between primaries and metastases were in FBN2 and MMP3, which showed over a 7-fold difference. In addition, we uncovered two distinct subtypes of CRC metastases that are characterized by either EMT-inflammatory or proliferative phenotypes, and demonstrated that none of the metastases examined were of consensus molecular subtype (CMS) 3 suggesting subtype exclusivity. Highlighting transcriptome differences between primary tumors and CRC metastases delineates pathways that may be activated in metastases and may assist in the development and/or selection of existing targeted treatment regimens for individuals with metastatic disease.
2019-05-18 | GSE131418 | GEO
Project description:Lung cancer is the leading cause of cancer-related deaths worldwide and lung adenocarcinoma is the most common form of lung cancer. Genomic studies of lung adenocarcinoma (LUAD) have advanced our understanding of the disease's biology and accelerated targeted therapy. However, the proteomic characteristics of LUAD are still insufficiently understood. Prognosis for lung cancer patients remains poor and is strongly related to the stage of disease at the time of diagnosis. Therefore, our study focuses on metastasis formation in LUAD. We performed high-performance liquid chromatography (HPLC) and electrospray ionization tandem mass spectrometry (ESI-MS/MS) on a total of 40 FFPE samples and compared proteomic profiles of primary tumors to those of matched distant metastases. Using differential expression analysis and unsupervised clustering we identified candidate proteins playing a role in metastatic spread. Selected proteins were validated by immunoblotting. Our findings give a better understanding of tumor progression and metastasis formation in LUAD and might help to develop biomarker specific therapy.
2023-11-28 | PXD042604 | Pride
Project description:We have analysed a unique tumour set of fourteen primary breast cancer tumours with matched synchronous axillary lymph node metastases and a set of nine primary tumours with, later developed, matched distant metastases spread to different sites in the body. The aim was to further understand the molecular changes during the spreading and identify differentially regulated proteins that may be novel biomarkers or treatment targets. We analysed the changes in glycoprotein expression since protein glycosylation is predominant in both membrane proteins and secreted proteins and these proteins are often important for cancer transformation. This may also allow affinity capture enabling selected reaction monitoring of these biomarkers in blood. Glycopeptide capture was used in this study to selectively isolate and quantify N-linked glycopeptides from tumours mixtures and the captured glycopeptides were subjected to label-free quantitative tandem mass spectrometry analysis. Differentially expressed proteins between primary tumours and matched lymph node metastasis and distant metastasis were identified. Two of the top hits, ATPIF1 and tubulin β-chain were validated to be differentially regulated with immunohistochemistry.
2022-02-28 | PXD001637 | Pride
Project description:This study is to compare DNA methylation profiles between primary NSCLCs and paired distant metastases.
| EGAS00001004079 | EGA
Project description:To investigate the exosomal miRNA changes under LPS treatment in RAW 264.7 cells, 2 μg/mL LPS were added into complete medium to incubate RAW 264.7 cells. And then The exosomes were isolated and tested the exosomal miRNAs change using microarray.
2023-04-30 | GSE149630 | GEO