Clinical Impact of Exosomes in Colorectal Cancer Metastasis

Abstract

Cancer is a complex deadly disease that has caused a global health crisis in recent epochs. Colorectal cancer (CRC) is the third most common malignant gastrointestinal disease. It has led to high mortality due to early diagnostic failure. Extracellular vesicles (EVs) come with promising solutions for CRC. Exosomes (a subpopulation of EVs) play a vital role as signaling molecules in CRC tumor microenvironment. It is secreted from all active cells. Exosome-based molecular transport (DNA, RNA, proteins, lipids, etc.) transforms the recipient cell’s nature. In CRC, tumor cell-derived exosomes (TEXs) regulate multiple events of CRC development and progression such as immunogenic suppression, angiogenesis, epithelial–mesenchymal transitions (EMT), physical changes in the extracellular matrix (ECM), and metastasis. Biofluid-circulated tumor-derived exosomes (TEXs) are a potential tool for CRC liquid biopsy. Exosome-based colorectal cancer detection creates a great impact in CRC biomarker research. The exosome-associated CRC theranostics approach is a state-of-the-art method. In this review, we address the CRC and exosomes complex associated with cancer development and progression, the impact of exosomes on CRC screening (diagnostic and prognostic biomarkers), and also highlight several exosomes with CRC clinical trials, as well as future directions of exosome-based CRC research. Hopefully, it will encourage several researchers to develop a potential exosome-based theranostic tool to fight CRC.

Clinical Theragnostic Signature of Extracellular Vesicles in Traumatic Brain Injury (TBI)

“…There are two distinct mechanisms by which exosomes are produced: ESCRT (Endosomal Sorting Complexes Required for Transport)-dependent and ESCRT-independent . ILVs are produced by ESCRT using a sophisticated networking cascade − involving four types of complexes such as ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III. − In the initial stages of the pathway, ESCRT-0 binds to Zinc Finger Domains (ZFDs) and Ubiquitin-Interacting Motifs (UIMs), present in the plasma membrane through its dimeric subunits like hepatocyte growth factor regulated tyrosine kinase substrate (HRS) and signal-transducing adaptor molecule 1/2 (STAM-1/2) . This subsequently activates ESCRT-I and ESCRT-II, which facilitate cytoplasmic budding from the plasma membrane being guided by ESCRT-0, followed by mediation of cargo selection by ESCRT-II and ESCRT-III …”

“… , The next level of complexity lies in exosome toxicity. Exosome toxicity needs more clear scientific investigation for affordable and efficient exosome-based therapeutic approach development for TBI. ,− Therefore, it is important to develop standardized methods for EVs isolation, purification, and analysis to ensure the reproducibility and comparability of results across different studies …”

Unlocking Exosome-Based Theragnostic Signatures: Deciphering Secrets of Ovarian Cancer Metastasis

“…They contribute to intracellular communication . Exosome-based molecular transport (DNA, RNA, and proteins) transforms the nature of the recipient cell. , In the cellular system, the maturation and secretion of exosomes go through several stages such as early endosome, late endosome, intraluminal vesicle (ILV), and multivesicular bodies. , The biogenesis of exosomes is classified into two pathways: ESCRT-dependent and ESCRT-independent. − ESCRT-dependent pathways are regulated via the ESCRT complex (ESCRT-0 to ESCRT-III) . The ESCRT-independent pathway is regulated via a cytoplasmic molecular response, with ceramide playing a vital role in MVB fusion with the plasma membrane and the release of exosomes .…”

Clinical Theranostics Trademark of Exosome in Glioblastoma Metastasis

“…ESCRT complex-independent exosome biogenesis is involved in two molecular mechanisms such as the ceramide-and tetraspaninmediated pathway (it is further divided into two subdivisions, one CD63-associated and another CD9-and CD82-associated). 18 In the cellular system, sphingomyelinase hydrolyzes sphingomyelin to develop ceramide, supports the fusion of MVB with the plasma membrane, and releases exosomes. 25 In cancer cells, release of exosomes is dependent on CD63-mediated signaling pathways.…”

“…During exosome biogenesis, MVBs fuse with the plasma membrane and release exosomes . MVB transport is associated with two ways such as ESCRT-dependent and ESCRT-independent processes. , These molecular cascades are associated with exosome biogenesis. The endosome sorting complex required for transport (ESCRT) plays a dynamic role in cellular systems such as cell death, apoptosis, vesicle budding, , cell signaling, autophagy, etc.…”