Exosomes in Prostate Cancer: Putting Together the Pieces of a Puzzle

Abstract

Exosomes have been shown to act as mediators for cell to cell communication and as a potential source of biomarkers for many diseases, including prostate cancer. Exosomes are nanosized vesicles secreted by cells and consist of proteins normally found in multivesicular bodies, RNA, DNA and lipids. As a potential source of biomarkers, exosomes have attracted considerable attention, as their protein content resembles that of their cells of origin, even though it is noted that the proteins, miRNAs and lipids found in the exosomes are not a reflective stoichiometric sampling of the contents from the parent cells. While the biogenesis of exosomes in dendritic cells and platelets has been extensively characterized, much less is known about the biogenesis of exosomes in cancer cells. An understanding of the processes involved in prostate cancer will help to further elucidate the role of exosomes and other extracellular vesicles in prostate cancer progression and metastasis. There are few methodologies available for general isolation of exosomes, however validation of those methodologies is necessary to study the role of exosomal-derived biomarkers in various diseases. In this review, we discuss “exosomes” as a member of the family of extracellular vesicles and their potential to provide candidate biomarkers for prostate cancer.

Exosomes as divine messengers: are they the Hermes of modern molecular oncology?

“…2 Interestingly, recent studies have discovered that transformed-tumor cells can take advantage of these endogenous 'trafficking systems' by transferring molecules that activate cancer-related pathways such as anti-apoptotic, proliferative or other tumorigenic ones. Initially, malignant tumor cells develop and proliferate in their local niche through the activation of endogenous oncogenic proteins and pathways.…”

“…33 However, it was recently proven that vesicles released by cells could be indicative of the cell type and/or its function. 2,14 With the progression of exosomal-related studies, these vesicles have now become a useful tool with diagnostic utility, and a novel strategy to develop highly specific drug delivery systems.…”

“…17 Furthermore, their trafficking is cell specific, 18,19 and the exosomal content of the vesicles is highly regulated by a group of proteins that together form the endosomal sorting complex required for transport (ESCRT). 2,3 This complex determines the relative abundance of proteins, mRNA, 20 miRNAs (...and so on), that will be segregated into a vesicle to be further transported elsewhere.…”

“…Several key elements have been shown to be sequestered and transported through these vesicles: cytokines, growth factors, proteins, lipids, messenger RNAs (mRNAs) or noncoding transcripts, including microRNAs (miRNAs). [2][3][4][5] MiRNAs are short single-stranded (19)(20)(21)(22)(23)(24)(25) nucleotides in length) nonprotein-coding RNA transcripts (ncRNA) that are initially produced in the nucleus and then transported into the cytoplasm, where they undergo a series of steps to acquire maturation. Mature miRNAs regulate gene expression by binding (through watsonian complementarity) to the sequence of a target mRNA.…”

The use of molecular imaging combined with genomic techniques to understand the heterogeneity in cancer metastasis

“…91 In this context, exosomes are 40-to 100-nm-diameter membrane vesicles of endocytic origin that have been demonstrated to contain mRNA, miRNA and proteins, and are gaining increasing interest in terms of their translational research potential in cancer. [92][93][94][95][96] They are released into the extracellular space from various cell types and body fluids and mediate intercellular transfer of RNAs and proteins. As such, exosome analysis is ideally suited for monitoring the evolving tumour longitudinally, in terms of its whole transcriptome, miRNome and proteome profiles.…”