Abstract

Tumor-secreted extracellular vesicles (EVs) are the main mediators of cell-cell communication, permitting cells to exchange proteins, lipids, and metabolites in varying physiological and pathological conditions. They contain signature tumor-derived molecules that reflect the intracellular status of their cell of origin. Recent studies have shown that tumor cell-derived EVs can aid in cancer metastasis through the modulation of the tumor microenvironment, suppression of the immune system, pre-metastatic niche formation, and subsequent metastasis. EVs can easily be isolated from a variety of biological fluids, and their content makes them useful biomarkers for the diagnosis, prognosis, monitorization of cancer progression, and response to treatment. This review aims to explore the biomarkers of cancer cell-derived EVs obtained from liquid biopsies, in order to understand cancer progression and metastatic evolution for early diagnosis and precision therapy.

Highlights

  • Carcinogenesis is a process in which unlimited/uncontrolled cell division occurs, leading to the formation of malignant tumors

  • tumor microenvironment (TME) could promote the development of cancer-associated mesenchymal stem cells (CA-MSCs) with the ability to differentiate into Cancer-associated fibroblasts (CAFs) and influence cancer cells by secreting various metabolites by extracellular vesicles (EVs)

  • Limitations in sample quality, EV isolation methods, cargo analysis, and interpretation of results may contribute to the failure of them as biomarkers in achieving clinical utility

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Summary

Introduction

Carcinogenesis is a process in which unlimited/uncontrolled cell division occurs, leading to the formation of malignant tumors. EVs constitute a heterogeneous vesicle population secreted by virtually all cell types They have been found in many body fluids, including blood [4], urine [5], saliva [6], bronchoalveolar lavage [7], and cerebrospinal fluid [8]. Apoptotic bodies (1–5 μm in diameter) are released during the last steps of apoptosis through formation of membrane protrusions, such as microtubule spikes, apoptopodia, and beaded-apoptopodia These classifications have been widely used in the literature, it is advised to use this nomenclature sparingly. EVs are involved in different stages of tumorigenesis and metastasis by increasing angiogenesis and remodeling the extracellular matrix This activity allows cells to escape from immune system recognition and induces resistance to various cancer therapies [14,15]. We will highlight the best practices for identification of tumor biomarkers by cancer cell-derived EVs, placing an emphasis on the hallmarks of cancer, promotion of invasion, and metastasis

EVs Performing Multiple Functions in Cancer Formation
Angiogenesis
EVs in Promoting Metastasis Initiation and Progression
EVs in Immunomodulation
EVs in Reprogramming Energy Metabolism
EV Isolation from Different Body Fluids in Cancer
Serum and Plasma
Saliva
Studies of the Molecular Profiling of EVs as Potential Biomarkers
Proteome Profiling Analysis of EVs in Multiple Cancers
Lipidome Profiling Analysis of EVs in Multiple Cancers
Metabolome Profiling Analysis of EVs in Multiple Cancers
Findings
Future Challenges and Conclusions
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