In recent years, extracellular vesicles (EVs) have attracted attention due to their role as intercellular messengers. Research on the use of EVs in therapeutic applications, as drug delivery agents, and as disease biomarkers for disorders, such as cancer, is now evolving rapidly.
What are extracellular vesicles?
Extracellular vesicles or EVs are nanometer-sized lipid bilayer vesicles secreted by almost all cell types. Initially believed to be used as a means of disposing of waste by cells, researchers have gained a lot of knowledge regarding the importance of EVs in several applications. Both healthy and diseased cells produce EVs, which are present in a variety of body fluids, including blood, urine, saliva, interstitial fluid, and cerebrospinal fluid. They play a crucial role in intercellular communication by transferring bioactive cargo between cells.
fluid, and cerebrospinal fluid. They play a crucial role in intercellular communication by transferring bioactive cargo between cells.
EVs contain a heterogeneous mixture of lipids, nucleic acids, proteins, and metabolites as their cargo. They are divided mainly into three subtypes: exosomes, microvesicles, and apoptotic bodies, based on their size and generation mechanism. All of these EV subtypes are eventually released into the extracellular matrix.
Exosomes (30-100 nm) contain a variety of molecules, including proteins, lipids, nucleic acids (such as mRNA and microRNAs), and other signaling molecules. These cargoes can be transferred to recipient cells, where they can alter cellular functions and influence various physiological and pathological processes. Microvesicles (50-1000 nm) are larger than exosomes and are formed by the outward budding of plasma membranes. They carry a similar cargo as exosomes, including proteins, lipids, and nucleic acids and can also transfer their contents to recipient cells and participate in intercellular communication. Apoptotic bodies (1000-5000 nm) are released during programmed cell death (apoptosis) and contain cellular components from the dying cell, including organelles, DNA, RNA, and proteins. They are removed by phagocytic cells, allowing for the removal of cellular debris and the maintenance of tissue homeostasis.
EVs are implicated in various physiological processes, such as immune response modulation, tissue repair, and cell-to-cell communication. Additionally, their presence in biofluids makes them attractive candidates for non-invasive monitoring of diseases, including cancer, neurodegenerative disorders, and cardiovascular diseases.
Why are EVs from the tumor microenvironment important to study?
The tumor microenvironment consists of various cell types, including cancer cells, stromal cells, immune cells, and blood vessels. EVs released by tumor cells and other components of the microenvironment contribute to tumor growth, metastasis, and immune evasion. Here are some key roles of EVs in the tumor microenvironment:
Intercellular Communication:
EVs facilitate communication between tumor cells and neighboring cells within the microenvironment by transferring bioactive cargoes. These cargo molecules can modulate cellular processes, promote angiogenesis (the formation of new blood vessels to supply nutrients to the tumor), and facilitate tumor invasion and metastasis.
Immune Regulation and Metastasis:
EVs released by tumor cells can exert immunosuppressive effects, allowing tumors to evade immune surveillance. Tumor-derived EVs can carry molecules that inhibit immune responses, such as regulatory proteins and microRNAs that suppress immune cell function. They can also induce the differentiation of immune cells into suppressive or pro-tumor phenotypes, impairing the anti-tumor immune response. Through the transfer of certain biomolecules, EVs can directly impact the behavior of endothelial cells, which are responsible for the formation of angiogenesis or new blood vessels that are known to play a role in tumor progression. EVs are involved in various aspects of tumor progression and metastasis. They can promote epithelial-mesenchymal transition (EMT), a process that enhances the invasive and migratory properties of cancer cells.
Diagnostic and Prognostic Biomarkers:
The presence of specific EVs and their cargo molecules in body fluids can serve as diagnostic and prognostic biomarkers for cancer. By analyzing the composition of EVs, including their proteins, nucleic acids, and other molecules, researchers can gain insights into the molecular characteristics of tumors and monitor disease progression.
Therapeutic Delivery:
EVs hold promise as vehicles for delivering therapeutic molecules to tumor cells. They can be engineered to carry specific cargoes, such as anti-cancer drugs, small interfering RNAs (siRNAs), or gene-editing tools. These engineered EVs can be targeted at tumor cells, enabling efficient delivery of therapeutic agents while minimizing off-target effects.
Understanding the roles of extracellular vesicles in the tumor microenvironment is crucial for developing effective strategies to diagnose and treat cancer. Research in this field aims to exploit the diagnostic and therapeutic potential of EVs while also unraveling their complex interactions within the microenvironment to develop targeted therapies that disrupt tumor progression.
The clinical importance of EVs in monitoring various diseases, including cancer, and developing targeted therapies, is well established. However, the extraction and isolation of EVs in their pure form still pose a challenge due to a lack of standardization in processes. Also, the extraction of EVs from the blood stream represents only a small component of the EVs at the tumor source. Further, EVs from cultured tumor cells may not have the same composition as EVs taken from live tissues, which means they would not give a complete picture of the tumor microenvironment.
Targeted Bioscience’s Targeted EV™ Interstitial Fluid and Extracellular Vesicle Isolation Kit offers a highly efficient method to harvest EVs from the interstitial fluid (IF) without affecting the viability or morphology of the tissue cells. The one-step protocol can efficiently extract extracellular vesicles of all subtypes. Interstitial fluid from the tumor tissues establishes an essential communication channel between the tumor and the sentinel draining lymph node, which facilitates the immune invasion of the tumor. As IF EVs provide an accurate snapshot of the tumor microenvironment, they are a valuable source of previously untapped insights. Targeted Bioscience’s Targeted EV™ Interstitial Fluid and Extracellular Vesicle Isolation Kit can help unravel the tissue IF’s secrets and accelerate translational and clinical research to advance precision medicine.
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References
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678302/#:~:text=Extracellular%20vesicles%20(EVs)%20are%20lipid,1%2C2%2C3%5D.
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352700/#:~:text=EVs%20participate%20in%20cancer%20progression,in%20local%20and%20distant%20microenvironments.
- https://pubmed.ncbi.nlm.nih.gov/27505671/.
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168913/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602830/#:~:text=Extracellular%20vesicles%20(EVs)%20exert%20their,cell%2Dto%2Dcell%20communication.
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008708/#:~:text=Extracellular%20vesicles%20(EVs)%20produced%20by,increase%20invasive%20and%20metastatic%20activity
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555429/
- https://www.sciencedirect.com/science/article/pii/S0753332222008691#sec0005
- https://biosignaling.biomedcentral.com/articles/10.1186/s12964-020-00643-5