Circulating Exosomes and Microvesicles as Biomarkers of Cancer
Exosomes are small vesicles (50-100 nm) secreted by almost all tissues; they represent their tissue of origin. Exosomes although used synonymously are distinguished from microvesicles which are heterogeneous in size (50-1500 nm) and shed directly from the budding of the plasma membrane. Tumor cells release an abundance of exosomes and microvesicles containing a selected set of proteins and RNAs. Exosomes are valuable sources for biomarkers due to selective cargo loading and resemblance to their parental cells. It has been shown that tumor microvesicles and exosomes also carry DNA, which reflects the genetic status of the tumor, including amplification of the oncogene c-Myc (Balaj et al. 2011). This study also found amplified c-Myc in serum microvesicles from tumor-bearing mice. Further, the authors found remarkably high levels of retrotransposon RNA transcripts, especially for some human endogenous retroviruses, such as LINE-1 and Alu retrotransposon elements, in tumor microvesicles and these transposable elements could be transferred to normal cells. These findings expand the nucleic acid content of tumor microvesicles to include: elevated levels of specific coding and non-coding RNA and DNA, mutated and amplified oncogene sequences and transposable elements. Thus, tumor microvesicles or exosomes contain a repertoire of genetic information available for horizontal gene transfer and potential use as biomarkers for cancer in circulating blood.
Cancer-derived exosomes contribute to cancer progression by enhancement of intercellular transfer of cargo that contains proteins, lipids and nucleic acids within the tumor microenvironment. This reflects the altered state of original cancers, making exosomes as biomarkers for early detection, diagnosis and prognosis with higher sensitivity and specificity compared to conventional biopsy or other liquid biopsy biomarkers (Soung et al. 2017). The value of exosomes as biomarkers for breast cancer, prostate cancer, pancreatic cancer, and glioblastoma multiforme is described in sections dealing with these cancers.
Circulating miRNAs for Cancer Detection
miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. Measurement of tumor-derived miRNAs in serum or plasma is an important approach for the blood-based detection of human cancer. Locked nucleic acid (LNA) is a conformational RNA analog that binds to RNA with unprecedented affinity and specificity, making it well suited for miRNA detection and analysis for cancer diagnostics (Stenvang et al. 2008).