Secreted factors promote angiogenesis and invasion, aiding in tumor growth and progression. Communication between cancer cells and the microenvironment is likely mediated in part by exosomes, both secreted

Linsitinib solubility by cancer cells and the microenvironment itself. Stromal secreted exosomes promote breast cancer motility and metastasis[38]. Tumor secreted exosomes can promote endothelial tubule formation[39], as well as secrete matrix metalloproteinases, aiding in invasion[40]. Molecular changes in tumor stroma are an important part of breast cancer initiation and progression[37]. Exosomes can suppress immune response by promoting T regulatory cell expansion and inducing apoptosis of effector T cells[41]. In tumor cells exosomes mediate upregulation of anti-apoptotic genes and anchorage independent growth[42], and are believed to be involved in resistance to drug and radiation resistance[32]. Exosomes transfer their contents to receiving cells via internalization of the exosome. Heparan sulfate proteoglycans are necessary receptors of cancer cell derived exosomes, and are necessary for exosome uptake and delivery of macromolecular contents[43]. A precise method for identifying tumor secreted exosomes is not yet available. Tumor secreted exosomes are differentiated by analysis of their contents. Proteins

and miRNA found in exosomes closely match those in the parent cell. In some cases, FACS can be conducted using antibody for tumor specific protein in exosomes, such as HER2/neu[44]. Marker proteins that are often overexpressed in tumors are found in exosomes, including EpCAM, CD24, L1CAM, CD44 and EGFR. The utility of these markers for identification of tumor-secreted exosomes is under investigation[45]. Exosomal miRNAs Breast cancer

heterogeneity is reflected in tumor-secreted exosomes. While miRNA sequencing of secreted breast cancer exosomes is still in its infancy, exosomal miRNA expression from other diseases exhibit a high level of correlation to parental cells[46]. Exosomes have been successfully isolated from many sources in the body, including blood plasma, serum and urine[32]. Due to their ubiquity and disease specific GSK-3 expression, there is significant potential for exosomal use as biomarkers of disease state or progression[36]. MiRNA array shows differential expression of miR-140 between DCIS stem-like and DCIS whole cell populations. Similarly, miR-140 is downregulated in exosomes derived from DCIS stem-like cells compared to exosomes derived from DCIS whole cell population. Exosomal levels of miR-140 from stem cell populations can be rescued by treatment with sulforaphane. Treatment of invasive basal like breast cancer cells and DCIS cells with miR-140 containing exosomes resulted in an increased level of miR-140 in both cell lines, demonstrating the potential of exosomal secretion to impact miR-140 signaling in nearby cells.