Extracellular vesicles in glioblastoma – a challenge and an opportunity

Understanding the Dual Role of Extracellular Vesicles in Glioblastoma

Glioblastoma is one of the most aggressive and complex brain tumors, characterized by its high heterogeneity. This means that the tumor contains a mix of different types of cancer cells, each with its own characteristics. This complexity makes diagnosing and treating glioblastoma particularly challenging. Traditional diagnostic methods and treatment options have not been very successful in managing this disease. Researchers at Aarhus University discuss the contrasting yet interdependent dual role of extracellular vesicles as communication agents that contribute to the progression of glioblastoma by creating a heterogeneous microenvironment and as a liquid biopsy tool providing an opportunity to accurately identify the disease severity and progression.

The Challenge of Glioblastoma

Glioblastoma’s heterogeneous nature means that standard diagnostic tools often fail to capture the full scope of the tumor’s complexity. This leads to difficulties in accurately determining the severity of the disease and predicting how well a patient will respond to therapy. As a result, patients often receive treatments that are not optimally tailored to their specific type of glioblastoma, which can lead to less effective outcomes.

The Promise of Extracellular Vesicles

Extracellular vesicles (EVs) are tiny particles released by cells that play a crucial role in cell-to-cell communication. These vesicles carry proteins, RNA, and other molecules from their cell of origin to other cells, influencing their behavior. In recent years, researchers have discovered that EVs can serve as a promising tool in the fight against glioblastoma, offering new insights and opportunities for diagnosis and treatment.

EVs: Agents of Communication and Complexity

Interestingly, EVs have a dual role in glioblastoma. On one hand, they contribute to the tumor’s progression. EVs released by glioblastoma cells can interact with other cells in the tumor microenvironment, promoting growth and creating a more complex and supportive environment for the tumor. This communication helps the tumor become more aggressive and resistant to therapies.

EVs as Liquid Biopsy Tools

On the other hand, EVs also hold great potential as a diagnostic tool. Because they carry molecular information from their parent cells, EVs can provide a snapshot of the tumor’s characteristics. By analyzing EVs found in bodily fluids like blood, researchers can gain valuable insights into the nature of the glioblastoma without needing to perform invasive tissue biopsies. This process, known as a liquid biopsy, can help doctors more accurately determine the severity of the disease and monitor its progression over time.

Schematic representation showing both the challenging scenario and opportunity presented by extracellular vesicles (EVs) in glioblastoma

Fig. 2

EVs secreted by glioblastoma cells and other surrounding cells within the heterogeneous tumor microenvironment (TME) mediate communication and facilitate transport of pro-tumorigenic molecules between cells contributing to further tumor progression, which is a significant challenge. However, the EVs involved in intercellular communication within the glioblastoma microenvironment can cross the blood-brain barrier (BBB) and be found in systemic circulation. Circulating EVs can be isolated by suitable methodologies and profiled to understand the status and severity of the glioblastoma, providing a significant opportunity to utilize EVs both as biomarkers for disease diagnosis and to monitor response to treatment. In diagram abbreviations; EVs (Extracellular Vesicles); TME (Tumor microenvironment); BBB (blood-brain barrier); (A) represents the activated state; and (H) represents the hypoxic state.

Bridging the Gap in Glioblastoma Diagnosis and Treatment

The dual nature of EVs as both contributors to glioblastoma progression and as tools for diagnosis presents a unique opportunity. By understanding how EVs facilitate tumor growth and using them to gather detailed information about the tumor, researchers can develop better diagnostic methods and more targeted therapies. This could lead to more personalized treatment plans, improving outcomes for patients with glioblastoma.

Conclusion

The study of extracellular vesicles is opening new doors in the fight against glioblastoma. While these vesicles contribute to the tumor’s complexity and progression, they also offer a powerful tool for diagnosis and monitoring. By harnessing the potential of EVs, we can improve our understanding of glioblastoma and develop more effective strategies to combat this challenging disease.

Indira Chandran V, Gopala S, Venkat EH, Kjolby M, Nejsum P. (2023) Extracellular vesicles in glioblastoma: a challenge and an opportunity. NPJ Precis Oncol 8(1):103. [article]

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