Abstract
Brain metastases represent more than 50% of all cerebral tumors encountered in clinical practice. Recently, there has been increased interest in the study of extracellular vesicles, and the knowledge about exosomes is constantly expanding. Exosomes are drivers for organotropic metastatic spread, playing important roles in the brain metastatic process by increasing the permeability of the blood–brain barrier and preparing the premetastatic niche. The promising results of the latest experimental studies raise the possibility of one day using exosomes for liquid biopsies or as drug carriers, contributing to early diagnosis and improving the efficacy of chemotherapy in patients with brain metastases. In this review, we attempted to summarize the latest knowledge about the role of exosomes in the brain metastatic process and future research directions for the use of exosomes in patients suffering from brain metastatic disease.
Highlights
Cerebral metastatic disease is one of the most feared complications of cancer, and brain metastasis represents more than 50% of all brain tumors seen clinically
The release and upalso favored by as occurs the development thebepremetastatic niche by hypoxia, as hypoxia, occurs the development of the premetastatic niche in Exosomal take of exosomes are accelerated ininacidic pHin environments, as of can found the priExosomal uptake is performed through various mechanisms, including phagocytosis, uptake is performed through various mechanisms, including phagocytosis, membrane mary tumor microenvironment [26]
A premetastatic niche describes the formation of a specific microenvironment in a distant organ that is devoid of cancer cells, and this process is induced by the primary tumor, which releases various tumor factors and small EVs that travel to secondary organs where they remodel the extracellular matrix, modify the vascular permeability, and alter the immune system by fusing with the resident cells and transferring their cargo of proteins, various metabolites, or genetic material
Summary
Cerebral metastatic disease is one of the most feared complications of cancer, and brain metastasis represents more than 50% of all brain tumors seen clinically. Organotropism is the organ specificity of metastases dictated by tumor-derived small EVs, which even today raises many unanswered questions [9] These small, single-membrane extracellular vesicles that are released by all cell lineages in the human body in a healthy or a pathological state play an important role in noncanonical intercellular communication, among other roles [10]. Their lipid bilayer allows them to safely travel within the bloodstream and join with their target cells [11,12]. Each method has its advantages and disadvantages, but the purest small EVs samples can be obtained by ultracentrifugation and density gradient purification, this method offers a decreased yield [21]
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