International Journal of Biological and Biomedical Research

The Role of Exosomes in Tumor Microenvironment Remodeling and Cancer Metastasis: A Review

Nebras Rada Mohammed¹, Mamoon Abdulmajeed Ibrahim²

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Abstract

Molecular changes within the cancer cells are not enough to explain the metastatic potential of malignant tumors. The communication between the malignant cells and their cellular and extracellular milieu is crucial for the progression of the tumor. The mediators that participate in this communication have received a lot of attention in recent years, not only for the biological activity they carry but also because of their ability to trans-fer biologically active material from one cell population to the other, notably exosomes and other small extracellular vesicles. These vesicles can carry proteins, lipids, messenger RNAs, microRNAs, long non-coding RNAs, circular RNAs, enzymes and other signalling molecules that can aid in changing the phenotype of the recipient cells. In the tumor microenvironment, exosome mediated signalling can activate fibroblasts, induce metabolic adaptation, induce angiogenesis, cause endothelial dysfunction, immune escape, epithelial–mesenchymal plasticity and extracellular matrix remodeling. Their impact is not confined to the primary tumor, as tumour-derived vesicles in circulation can also modulate distant tissues, and aid in the formation of pre-metastatic niches before metastasis can occur. Exosomes have also been shown to be secreted by stromal cells, such as cancer associated fibroblasts and macrophages, which can further promote tumor cell migration, invasion and therapy resistance. These biological characteristics have led to their exploration as liquid-biopsy markers and as therapeutic targets and/or delivery systems. Although significant advances have been made, there are also important challenges, including vesicle heterogeneity, reproducibility, large-scale production methods, and extracellular-vesicle classification and isolation methods, as well as clinical validation. The current review explores the key pathways through which exosomes are involved in remodeling the tumor microenvironment and promoting metastasis, focusing on stromal reprogramming, vascular alterations, immune modulation, EMT and ECM alterations, and pre-metastasis niche formation. Current applications in diagnosis and treatment, methodological shortcomings and future research priorities are also critically examined.

Keywords: Exosomesextracellular vesiclestumour microenvironmentcancer metastasispre-metastatic nicheangiogenesisimmune escapecancer-associated fibroblastsepithelial–mesenchymal transition

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