Читать книгу Genomic and Epigenomic Biomarkers of Toxicology and Disease - Группа авторов - Страница 34

Exosomes were originally discovered in 1983, as membrane vesicles of approximately 100 nm in diameter with a lipid bilayer structure. These vesicles are secreted by reticulocytes (Harding and Stahl 1983; Pan and Johnstone 1983). They were initially thought to be a “trash bag” in which cells could eliminate excess proteins; however, from 2007 on great advances in exosome research were made, as it was shown that microRNAs (miRNAs) in exosomes could be transferred between cells and played important roles in many physiological and pathological processes (Valadi et al. 2007; Pegtel et al. 2010; Mittelbrunn et al. 2011; Hergenreider et al. 2012; Montecalvo et al. 2012).

Exosomes are secreted into body fluids from various types of cells and organs. Recent studies have demonstrated that exosomes secreted by tumor cells are transported to surrounding cells and participate in metastasis and infiltration. Since these tumor-derived exosomes containing cancer cell-specific miRNAs and mRNAs are secreted into body fluids such as blood, urine, ascites, amniotic fluid, bronchoalveolar lavage, and tears, the miRNAs and mRNAs in cancer cell-derived exosomes have come to be used as diagnostic biomarkers for early stage cancers (Thery et al. 2002; Logozzi et al. 2009; Lu et al. 2009; Rabinowits et al. 2009; Montecalvo et al. 2012; Peinado et al. 2012). In parallel, miRNAs contained in exosomes released into the blood from tissues and organs in response to adverse events, such as exposure to chemical substances and drugs, are expected to be useful as novel biomarkers for toxicity assessment.

In this chapter we will introduce the latest findings on exosomes, including the newly appreciated biological significance of exosomes, and will explain the potential use of exosomes as biomarkers of toxicity.