Selective release of microRNA species from normal and malignant mammary epithelial cells
MicroRNAs (miRNAs) in body fluids are candidate diagnostics for a variety of conditions and diseases, including breast cancer. One premise for using extracellular miRNAs to diagnose disease is the notion that the abundance of the miRNAs in body fluids reflects their abundance in the abnormal cells c...
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| creator | Pigati, Lucy Yaddanapudi, Sree C S Iyengar, Ravi Kim, Dong-Ja Hearn, Steven A Danforth, David Hastings, Michelle L Duelli, Dominik M |
| description | MicroRNAs (miRNAs) in body fluids are candidate diagnostics for a variety of conditions and diseases, including breast cancer. One premise for using extracellular miRNAs to diagnose disease is the notion that the abundance of the miRNAs in body fluids reflects their abundance in the abnormal cells causing the disease. As a result, the search for such diagnostics in body fluids has focused on miRNAs that are abundant in the cells of origin. Here we report that released miRNAs do not necessarily reflect the abundance of miRNA in the cell of origin. We find that release of miRNAs from cells into blood, milk and ductal fluids is selective and that the selection of released miRNAs may correlate with malignancy. In particular, the bulk of miR-451 and miR-1246 produced by malignant mammary epithelial cells was released, but the majority of these miRNAs produced by non-malignant mammary epithelial cells was retained. Our findings suggest the existence of a cellular selection mechanism for miRNA release and indicate that the extracellular and cellular miRNA profiles differ. This selective release of miRNAs is an important consideration for the identification of circulating miRNAs as biomarkers of disease. |
| doi_str_mv | 10.1371/journal.pone.0013515 |
| format | Article |
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One premise for using extracellular miRNAs to diagnose disease is the notion that the abundance of the miRNAs in body fluids reflects their abundance in the abnormal cells causing the disease. As a result, the search for such diagnostics in body fluids has focused on miRNAs that are abundant in the cells of origin. Here we report that released miRNAs do not necessarily reflect the abundance of miRNA in the cell of origin. We find that release of miRNAs from cells into blood, milk and ductal fluids is selective and that the selection of released miRNAs may correlate with malignancy. In particular, the bulk of miR-451 and miR-1246 produced by malignant mammary epithelial cells was released, but the majority of these miRNAs produced by non-malignant mammary epithelial cells was retained. Our findings suggest the existence of a cellular selection mechanism for miRNA release and indicate that the extracellular and cellular miRNA profiles differ. This selective release of miRNAs is an important consideration for the identification of circulating miRNAs as biomarkers of disease.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0013515</identifier><identifier>PMID: 20976003</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abundance ; Antigens ; Apoptosis ; Bioindicators ; Biology ; Biomarkers ; Body fluids ; Breast cancer ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cell Biology/Cell Signaling ; Cell Biology/Gene Expression ; Cell Biology/Membranes and Sorting ; Cell Line, Tumor ; Data analysis ; Epithelial cells ; Female ; Genetics and Genomics/Genetics of Disease ; Health risk assessment ; Hostages ; Humans ; Laboratories ; Malignancy ; Mammary gland ; Mammary Glands, Human - metabolism ; Medical diagnosis ; Medical research ; Medical schools ; Medicine ; Methods ; MicroRNA ; MicroRNAs ; MicroRNAs - metabolism ; Milk ; miRNA ; Oncology/Breast Cancer ; Pathology ; Polymerase chain reaction ; Ribonucleic acid ; RNA ; Science ; Womens health</subject><ispartof>PloS one, 2010-10, Vol.5 (10), p.e13515-e13515</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Pigati et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Pigati et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c723t-783175c7a563fb00e08b269be6fe9960a0929b684decd574d4e69811bb2134fd3</citedby><cites>FETCH-LOGICAL-c723t-783175c7a563fb00e08b269be6fe9960a0929b684decd574d4e69811bb2134fd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958125/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958125/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20976003$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pigati, Lucy</creatorcontrib><creatorcontrib>Yaddanapudi, Sree C S</creatorcontrib><creatorcontrib>Iyengar, Ravi</creatorcontrib><creatorcontrib>Kim, Dong-Ja</creatorcontrib><creatorcontrib>Hearn, Steven A</creatorcontrib><creatorcontrib>Danforth, David</creatorcontrib><creatorcontrib>Hastings, Michelle L</creatorcontrib><creatorcontrib>Duelli, Dominik M</creatorcontrib><title>Selective release of microRNA species from normal and malignant mammary epithelial cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>MicroRNAs (miRNAs) in body fluids are candidate diagnostics for a variety of conditions and diseases, including breast cancer. One premise for using extracellular miRNAs to diagnose disease is the notion that the abundance of the miRNAs in body fluids reflects their abundance in the abnormal cells causing the disease. As a result, the search for such diagnostics in body fluids has focused on miRNAs that are abundant in the cells of origin. Here we report that released miRNAs do not necessarily reflect the abundance of miRNA in the cell of origin. We find that release of miRNAs from cells into blood, milk and ductal fluids is selective and that the selection of released miRNAs may correlate with malignancy. In particular, the bulk of miR-451 and miR-1246 produced by malignant mammary epithelial cells was released, but the majority of these miRNAs produced by non-malignant mammary epithelial cells was retained. Our findings suggest the existence of a cellular selection mechanism for miRNA release and indicate that the extracellular and cellular miRNA profiles differ. This selective release of miRNAs is an important consideration for the identification of circulating miRNAs as biomarkers of disease.</description><subject>Abundance</subject><subject>Antigens</subject><subject>Apoptosis</subject><subject>Bioindicators</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Body fluids</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Biology/Cell Signaling</subject><subject>Cell Biology/Gene Expression</subject><subject>Cell Biology/Membranes and Sorting</subject><subject>Cell Line, Tumor</subject><subject>Data analysis</subject><subject>Epithelial cells</subject><subject>Female</subject><subject>Genetics and Genomics/Genetics of Disease</subject><subject>Health risk assessment</subject><subject>Hostages</subject><subject>Humans</subject><subject>Laboratories</subject><subject>Malignancy</subject><subject>Mammary gland</subject><subject>Mammary Glands, Human - 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One premise for using extracellular miRNAs to diagnose disease is the notion that the abundance of the miRNAs in body fluids reflects their abundance in the abnormal cells causing the disease. As a result, the search for such diagnostics in body fluids has focused on miRNAs that are abundant in the cells of origin. Here we report that released miRNAs do not necessarily reflect the abundance of miRNA in the cell of origin. We find that release of miRNAs from cells into blood, milk and ductal fluids is selective and that the selection of released miRNAs may correlate with malignancy. In particular, the bulk of miR-451 and miR-1246 produced by malignant mammary epithelial cells was released, but the majority of these miRNAs produced by non-malignant mammary epithelial cells was retained. Our findings suggest the existence of a cellular selection mechanism for miRNA release and indicate that the extracellular and cellular miRNA profiles differ. 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| subjects | Abundance Antigens Apoptosis Bioindicators Biology Biomarkers Body fluids Breast cancer Breast Neoplasms - metabolism Breast Neoplasms - pathology Cell Biology/Cell Signaling Cell Biology/Gene Expression Cell Biology/Membranes and Sorting Cell Line, Tumor Data analysis Epithelial cells Female Genetics and Genomics/Genetics of Disease Health risk assessment Hostages Humans Laboratories Malignancy Mammary gland Mammary Glands, Human - metabolism Medical diagnosis Medical research Medical schools Medicine Methods MicroRNA MicroRNAs MicroRNAs - metabolism Milk miRNA Oncology/Breast Cancer Pathology Polymerase chain reaction Ribonucleic acid RNA Science Womens health |
| title | Selective release of microRNA species from normal and malignant mammary epithelial cells |
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