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 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

Studies Of Sodium-22 Distribution During Hypothermia In Rattus Rattus

The response of regional circulation to reduced body temperature was studied in the white laboratory rat Rattus rattus, using injected 22Na as a tracer. Observations made on equilibration of plasma and tissue radiosodium, in normo- and hypothermic animals, provided evidence as to possible mechanisms responsible for transport of sodium at this interface. Evidence is also presented as to disposition of sodium in tissues during the first biological half-life. Circulation to the peritoneal cavity is reduced to 50%, and to skin and bone approximately 10% and 25% of normothermic values respectively at body temperatures of 16-18 C. The appearance of radiosodium in the heart and lungs is dependent upon circulation to the site of injection. Equilibration of plasma and tissue radiosodium in normothermic animals occurs within 1 hr of injection in all tissues except brain, femur, and spleen, which re­quire up to 12 hr. Transport of sodium between plasma and tissues appears to be affected primarily by diffusion or some related physical process