Increased serum levels of circulating exosomal microRNA-373 in receptor-negative breast cancer patients

// Corinna Eichelser 1, * , Isabel Stückrath 1, * , Volkmar Müller 2 , Karin Milde-Langosch 2 , Harriet Wikman 1 , Klaus Pantel 1 , Heidi Schwarzenbach 1 1 Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Germany 2 Clinic of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany * These authors contributed equally to this work Correspondence to: Heidi Schwarzenbach, e-mail: hschwarz@uke.uni-hamburg.de Keywords: cell-free miRs, exosomal miRs, estrogen receptor, luminal breast cancer Received: June 27, 2014      Accepted: August 28, 2014      Published: October 07, 2014 ABSTRACT In this study, we compared the blood serum levels of circulating cell-free and exosomal microRNAs, and their involvement in the molecular subtypes of breast cancer patients. Our analyses on cell-free miR-101, miR-372 and miR-373 were performed in preoperative blood serum of 168 patients with invasive breast cancer, 19 patients with benign breast diseases and 28 healthy women. MicroRNAs were additionally quantified in exosomes of 50 cancer patients and 12 healthy women from the same cohort. Relative concentrations were measured by quantitative TaqMan MicroRNA assays and correlated to clinicopathological risk factors. The concentrations of cell-free miR-101 (p=0.013) and miR-373 (p=0.024) were significantly different between patients with breast cancer and benign tumors. A prevalence of miR-101, miR-372 and miR-373 were found in exosomes. The levels of circulating exosomal (but not cell-free) miR-373 were higher in triple negative than luminal carcinomas (p=0.027). Also, estrogen-negative (p=0.021) and progesterone-negative (p=0.01) tumors displayed higher concentrations of exosomal miR-373 than patients with hormone-receptor positive tumors. Overexpression of miR-373 by transfection of MCF-7 cells showed downregulated protein expression of the estrogen receptor, and inhibition of apoptosis induced by camptothecin. Our data indicate that serum levels of exosomal miR-373 are linked to triple negative and more aggressive breast carcinomas.