Exosomal microRNAs in colorectal cancer: Overcoming barriers of the metastatic cascade (Review)

Abstract

The journey of cancer cells from a primary tumor to distant sites is a multi-step process that involves cellular reprogramming, the breaking or breaching of physical barriers and the preparation of a pre-metastatic niche for colonization. The loss of adhesion between cells, cytoskeletal remodeling, the reduction in size and change in cell shape, the destruction of the extracellular matrix, and the modification of the tumor microenvironment facilitate migration and invasion into surrounding tissues. The promotion of vascular leakiness enables intra- and extravasation, while angiogenesis and immune suppression help metastasizing cells become established in the new site. Tumor-derived exosomes have long been known to harbor microRNAs (miRNAs or miRs) that help prepare secondary sites for metastasis; however, their roles in the early and intermediate steps of the metastatic cascade are only beginning to be characterized. The present review article presents a summary and discussion of the miRNAs that form part of colorectal cancer (CRC)-derived exosomal cargoes and which play distinct roles in epithelial to mesenchymal plasticity and metastatic organotropism. First, an overview of epithelial-to-mesenchymal transition (EMT), metastatic organotropism, as well as exosome biogenesis, cargo sorting and uptake by recipient cells is presented. Lastly, the potential of these exosomal miRNAs as prognostic biomarkers for metastatic CRC, and the blocking of these as a possible therapeutic intervention is discussed.

Downregulation of exosomal miR-7-5p promotes breast cancer migration and invasion by targeting RYK and participating in the atypical WNT signalling pathway

“…Metastatic malignant breast cancer accounts for 20–30% of breast cancer cases and the survival rate of the disease is only 22%, making it the leading cause of death for patients [ 5 , 25 , 26 ]. Metastatic spread of breast cancer involves many steps, including EMT, migration, invasion, extravasation, mesenchymal–epithelial transformation (MET) and colonisation [ 27 ]. An increasing range of research has demonstrated the importance of exosomes for all metastatic processes such as migration invasion of cancer [ 28 , 29 ].…”

Tumor Microenvironment Shapes Colorectal Cancer Progression, Metastasis, and Treatment Responses

“…Exosomal microRNAs play pivotal pro- and anti-tumoral roles in CRC progression and metastasis. They could also serve as biomarkers of CRC progression in patients ( 96 , 97 ). On one hand, exosomal miR-21 promotes CRC cell proliferation, invasion, and therapy resistance ( 98 ).…”

Molecular Docking and Intracellular Translocation of Extracellular Vesicles for Efficient Drug Delivery

“…EV-mediated intracellular communication plays a role not only in maintaining cell homeostasis, but also in disease progression [ 96 , 97 , 98 , 99 ]. Exosomes are associated with several diseases, including cancer metastasis, which is the invasion and spread of primary cancer cells into other organs [ 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 ]. Exosomes have been shown to play an important role in the formation of the cancer microenvironment and the mechanisms of cancer malignancy, such as cancer cell growth, infiltration, metastasis, and pre-metastasis niche [ 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 ].…”