Exosomes

Exosomes are small extracellular vesicles (EVs) measuring 30-140 nm in diameter. They serve as carriers of functional molecules such as proteins, non-coding RNA, mRNA, and lipids. Acting as cellular messengers, exosomes have the ability to modulate the biological activity of recipient cells. Coined by Johnstone et al. in 1980, exosomes are described as tiny vesicles that retain similar enzymatic properties as their parent cells. They are formed through budding and the creation of multiple vesicles (MVBs), which then fuse with the plasma membrane (PM) and are subsequently released outside the cell. Moreover, exosomes can also be internalized via endocytosis within the cell, with their contents being delivered to target cells, thereby altering the cellular function.

Exosomes and Cancer

In comparison to normal cells, cancer cells produce and secrete a higher amount of proteins, nucleic acids, and lipids. These substances rely on exosomes as vehicles for intercellular transport, leading to the production of numerous tumor-associated exosomes. Typically measuring 30-100 nm in diameter, these exosomes are crucial mediators of the tumor microenvironment and play a significant role in cancer initiation and progression. They facilitate interactions between various cell types within the tumor microenvironment, serving as vital intercellular communication messengers during cancer cell metastasis and invasion.

Exosomes and the Tumor Microenvironment

Exosomes contribute to tumor proliferation and alterations in the tumor microenvironment during tumor development. In the process of promoting tumor growth, the biological macromolecules enclosed within exosomes are shielded by the lipid bilayer, protecting them from enzymatic degradation. Upon binding to receptors, tumor exosomes can modify the function and phenotype of recipient cells, subsequently influencing non-tumor cells and creating a conducive tumor microenvironment. Apart from promoting tumor cell proliferation, tumor-associated exosomes can induce angiogenesis, supply nutrients, aid in waste removal, facilitate cancer cell migration, and invasion.

Exosomes and Cancer Metastasis

Tumor cell dissemination involves multiple stages, including detachment from the primary site, invasion through the basement membrane, intravasation into the bloodstream, adaptation to secondary organs, and colonization. Exosomes play a pivotal role in mediating tumor cell migration by transferring key nucleic acid molecules from tumor cells to normal cells, thereby enhancing their invasive capabilities. Upon uptake by recipient cells, these exosomes can alter the phenotype of the recipient cells, creating a favorable pre-metastatic niche for tumor cell invasion and metastasis. Subsequently, exosomes regulate the external environment of tumor cells post-intravasation, promoting tumor cell colonization at distant sites.

Exosome-based Strategies for Cancer Treatment

Exosomes can serve as mediators for cancer treatment interventions, primarily by controlling cancer progression through the release of tumor-derived exosomes. Leveraging the natural molecular structure and unique biological functions of exosomes, they can be utilized as natural carriers for drug delivery. In inhibiting the release of tumor-derived exosomes, targeting Rab proteins has been identified as an effective approach. Additionally, blocking the uptake pathways of exosomes, such as clathrin-mediated endocytosis and phagocytosis, can impede the action of tumor-associated exosomes, leading to alterations in the tumor microenvironment and changes in receptor phenotypes, thereby inhibiting cancer progression. Utilizing exosomes as natural drug carriers capitalizes on their inherent structure, enabling them to bind to specific receptors and enhance drug delivery efficiency. Studies have demonstrated that engineering exosomes to encapsulate doxorubicin (Dox) and applying them to breast cancer cell lines can result in targeted drug delivery to tumor tissues, inhibiting tumor growth and achieving successful cancer treatment.

Challenges of Exosomes in Cancer Treatment

While exosomes offer significant advantages in cancer treatment, including enhanced drug delivery targeting and efficiency, their isolation and purification requirements are demanding. The presence of non-exosomal EVs can significantly reduce the efficacy of cancer treatment. Therefore, the field of cancer treatment is currently faced with the challenge of establishing standardized and rapid exosome isolation technologies. Moreover, attention must be paid to the cell source when utilizing exosomes for cancer treatment to prevent any alterations in the delivery characteristics of tumor exosomes that may promote cancer progression. Accurate characterization of exosomes also poses a challenge in the realm of cancer treatment.

References

1. Edgar, J.R. Q&A: What are exosomes, exactly? _BMC Biology_, 2016.

2. Henderson Meredith, Azorsa David. The Genomic and Proteomic Content of Cancer Cell-Derived Exosomes. _Frontiers in Oncology_, 2012.