Abstract
Colorectal cancer (CRC) ranks as the third leading cause of cancer mortality in both of men and women worldwide due to its metastatic properties and resistance to current treatment. Recent studies have shown that tumor-derived exosomes play emerging roles in the development of cancer. Exosomes are nano-sized extracellular vesicles (EVs) that contain lipids, proteins, DNAs, and RNA species (mRNA, miRNA, long non-coding RNA). These exosomal cargos can be transferred locally and systemically, after taken by recipient cells, so exosomes represent a new form of intercellular communication. There is increasing evidence demonstrating that exosomes control a wide range of pathways bolstering tumor development, metastasis and drug resistance. This review provides an in-depth and timely summary of the role of exosomes in CRC. We first describe the common features and biogenesis of exosomes. We then highlight important findings that support the emerging roles of exosomes in CRC cell growth, invasion and metastasis, as well as resistance to treatment. Finally, we discuss the clinical application of exosomes as diagnostic biomarkers, in vivo drug delivery system and the potential of novel exosome-based immunotherapy for CRC.
Highlights
extracellular vesicles (EVs), derived from various cells transfer information efficiently to recipient cells locally or systemically, play an important role in numerous biological activities [1]
There is increasing evidence demonstrating that exosomes control a wide range of pathways bolstering tumor development, metastasis and drug resistance
We discuss the clinical application of exosomes as diagnostic biomarkers, in vivo drug delivery system and the potential of novel exosome-based immunotherapy for Colorectal cancer (CRC)
Summary
EVs (extracellular vesicles), derived from various cells transfer information efficiently to recipient cells locally or systemically, play an important role in numerous biological activities [1]. After exposure to cancer cell-derived exosomes, epithelial cells with non-malignant phenotype received exosomal cargos, such as oncogenic mRNA or miRNA, and pro-angiogenic proteins, resulting in an altered biological property for tumor initiation [20, 21]. MiR-100 released by mutant KRAS CRC cells could further amplify miR-100 function in recipient wild-type cells as evidenced by the decreased expression of some target genes of miR-100 [23] These findings are important because they provide novel insight of the contributions of mutant KRAS exosomes to CRC. Recent reports from the Lyden’s laboratory showed that exosomes isolated from lung, liver- and brain-tropic tumor cells fuse preferentially with resident cells respectively at their predicted metastatic sites [34] Proteomic analysis of these exosome populations uncovered that unique intergrin expression patterns are the determining factors for this organotropism. The expression of miRNA-210 was markedly upregulated in exosomes as compared with its intracellular level in HCT8 cells, indicating its role in maintaining the growth-permissive microenvironment for primary cancer cells and guiding the new location for www.impactjournals.com/oncotarget
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