Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol. Jul;

Department of Obstetrics, Gynecology, and Women's Health, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Gynecologic Oncology (Impact Factor: 3.77). 08/2008; 110(1):13-21. DOI: 10.1016/j.ygyno.2008.04.033
Source: PubMed


Most ovarian cancer patients are diagnosed at an advanced stage (67%) and prospects for significant improvement in survival reside in early diagnosis. While expression patterns of a recently identified biomarker family, microRNA, appear to be characteristic of tumor type and developmental origin, microRNA profiling has been limited to tissue specimens. Tumors actively release exosomes into the peripheral circulation and we now demonstrate the association of microRNAs with circulating tumor-derived exosomes.
Circulating tumor exosomes were isolated using a modified MACS procedure with anti-EpCAM. Initially, microRNA profiles of ovarian tumors were compared to those of tumor exosomes isolated from the same patients. Levels of 8 microRNAs (miR-21, miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205 and miR-214) previously demonstrated as diagnostic, were compared in exosomes isolated from sera specimens of women with benign disease and various stages of ovarian cancer.
MicroRNA from ovarian tumor cells and exosomes from the same patients were positive for 218 of 467 mature microRNAs analyzed. The levels of the 8 specific microRNAs were similar between cellular and exosomal microRNAs (exhibiting correlations from 0.71 to 0.90). While EpCAM-positive exosomes were detectable in both patients with benign ovarian disease and ovarian cancer, exosomal microRNA from ovarian cancer patients exhibited similar profiles, which were significantly distinct from profiles observed in benign disease. Exosomal microRNA could not be detected in normal controls.
These results suggest that microRNA profiling of circulating tumor exosomes could potentially be used as surrogate diagnostic markers for biopsy profiling, extending its utility to screening asymptomatic populations.

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    • "In ovarian cancer, tumor cells release small cell-secreted vesicles called exosomes [2– 4]. Exosomes are endosome-derived vesicles (30–100 nm) that contain bioactive materials and are released by cells into the bloodstream [5], as well as urine [6], saliva [7] plasma [8], epididymal fluid [9], amniotic fluid [10], follicular fluid [11], malignant and pleural effusions of ascites [12], bronchoalveolar lavage fluid [13], synovial fluid [14], and breast milk [15]. Exosomes are also known to affect gene expression as Valadi and colleagues demonstrated RNAs in mast cell exosomes could be delivered to human and mouse mast cells leading to new protein production in recipient cells [2]. "
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    ABSTRACT: Epithelial ovarian cancer is the most aggressive and deadly form of ovarian cancer and is the most lethal gynecological malignancy worldwide; therefore, efforts to elucidate the molecular factors that lead to epithelial ovarian cancer are essential to better understand this disease. Recent studies reveal that tumor cells release cell-secreted vesicles called exosomes and these exosomes can transfer RNAs and miRNAs to distant sites, leading to cell transformation and tumor development. The RNA-binding protein LIN28 is a known marker of stem cells and when expressed in cancer, it is associated with poor tumor outcome. We hypothesized that high LIN28 expressing ovarian cancer cells secrete exosomes that can be taken up by nontumor cells and cause changes in gene expression and cell behavior associated with tumor development. IGROV1 cells were found to contain high LIN28A and secrete exosomes that were taken up by HEK293 cells. Moreover, exposure to these IGROV1 secreted exosomes led to significant increases in genes involved in Epithelial-to-Mesenchymal Transition (EMT), induced HEK293 cell invasion and migration. These changes were not observed with exosomes secreted by OV420 cells, which contain no detectable amounts of LIN28A or LIN28B. No evidence was found of LIN28A transfer from IGROV1 exosomes to HEK293 cells.
    11/2015; 2015(5):1-13. DOI:10.1155/2015/701390
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    • "For example, cancer cells secrete exosomes that appear capable of inducing oncogenic properties in recipient cells, including increased cell division or metastatic behaviour [28] [29] [30]. Consistent with findings that exosome levels are raised in the blood of cancer patients [29] [31], exosome-mediated signalling may underlie the cancer 'field effect', in which tumour cells have been shown to influence the phenotype of nearby cells [32]. Only recently light has been shed on the subcellular compartments and mechanisms involved in their biogenesis and secretion opening new avenues to understand their functions [27]. "
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    DESCRIPTION: Exosomes, ionising radiation, non-targeted effects of ionising radiation
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    • "Cancer cell lines are known to secrete significantly more EVs than noncancerous cell lines [59] [60] [61] [62] [63]. In line with this, serum from breast carcinoma (BrCa) patients contained significantly higher levels of exosomes than healthy donors [41] [64] [65]. "
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    ABSTRACT: The study of extracellular vesicles (EVs) in cancer progression is a complex and rapidly evolving field. Whole categories of cellular interactions in cancer which were originally presumed to be due solely to soluble secreted molecules have now evolved to include membrane-enclosed extracellular vesicles (EVs), which include both exosomes and shed microvesicles (MVs), and can contain many of the same molecules as those secreted in soluble form but many different molecules as well. EVs released by cancer cells can transfer mRNA, miRNA, and proteins to different recipient cells within the tumor microenvironment, in both an autocrine and paracrine manner, causing a significant impact on signaling pathways, mRNA transcription, and protein expression. The transfer of EVs to target cells, in turn, supports cancer growth, immunosuppression, and metastasis formation. This review focuses exclusively on breast cancer EVs with an emphasis on breast cancer-derived exosomes, keeping in mind that breast cancer-derived EVs share some common physical properties with EVs of other cancers.
    BioMed Research International 10/2015; 2015(19). DOI:10.1155/2015/634865 · 2.71 Impact Factor
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