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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Available from: Douglas D Taylor, Oct 04, 2015
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    • "Using miR-21, miR-141, miR-200a, miR-200c, miR- 200b, miR-205 and miR-214 as diagnostic miRNAs, the exosomal miRNA profiles highly reflect the tumor miRNA profiles. More importantly , the levels of these miRNAs in exosomes from plasma of ovarian cancer patients were significantly higher when compared to benign disease and could not be detected in normal controls, and differences in miR-200c and miR-214 expression with tumor stages [29], suggesting that the exosomal miRNA profile may not be limited to be used as a marker for early detection, but also in staging of ovarian carcinomas. "
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    ABSTRACT: The limitations of current chemotherapies have motivated research in developing new treatments. Growing evidences show that interaction between tumors and their microenvironment, but not tumor cells per se, is the key factor in tumor progression and therefore of obvious scientific interest and therapeutic value. Exosomes are small (30 to 100 nm) extracellular vesicles which have emerged as key mediators and communicators between cancer cells and other major cell types in the tumor microenvironment such as stromal fibroblasts, endothelial cells, and infiltrating immune cells as well as noncellular extracellular matrices through paracrine mechanisms. This review is to highlight the emerging role of exosomes in particular type of cancer, such as ovarian cancer, owing to its unique route of metastasis, which is capable of rapidly translating exosome research for clinical applications in diagnosis, prognosis, and potential treatment. Copyright © 2015. Published by Elsevier Ireland Ltd.
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    • "The study corroborated that cancer-specific signatures based on microRNA expression are shared both in cellular (tumor) and exosome (plasma) compartments of ovarian cancer patients [17]. Evidently, many miRNAs reported as the tumor markers may be found expressed abundantly in the blood plasma. "
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    • "Moreover, exosome production can be modulated by the tumor microenvironment (Ciravolo et al., 2012; Hedlund et al., 2011; King et al., 2012; Parolini et al., 2009). Their concentration in plasma can also be increased in patients with advanced stages of cancer (Logozzi et al., 2009; Taylor and Gercel-Taylor, 2008). Tumor exosomes can promote metastatic spread and hence disease progression by supporting evasion from immunosurveillance and by modifying signaling pathways via the transfer of growth factors/receptors, stimulation of angiogenesis, and microenvironment remodeling (Muralidharan-Chari et al., 2010). "
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