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This study reviewed the role of extracellular vesicles in renal cell carcinoma progression and their potential future clinical applications.

Extracellular vesicles (EVs) are nanosized vesicles released into the extracellular spaces by most cell types, including cancer and non-cancer cells. EVs secreted by renal cell carcinoma (RCC) play a role in various steps of cancer progression. A study in Nanomaterials has reviewed the mechanism by which RCC-derived EVs cause disease progression and their potential diagnostic and therapeutic implications.

Role of RCC-Derived Extracellular Vesicles in Cancer Progression and Drug Resistance

Clear-cell RCC is typically hypervascular and genetically characterized by Von Hippel-Lindau (VHL) gene inactivation. RCC-derived EVs contain microRNA (miRNA), which silences VHL mRNA. VHL protein inactivation leads to angiogenesis. Besides this pathway, RCC-derived EVs promote angiogenesis through the function of their cargo, such as exosomal carbonic anhydrase 9, miRNA, and aminopeptidase N.

RCC-derived EVs contribute to immune escape, a process by which tumor cells can evade immune surveillance. These EVs inhibit dendritic cell maturation and T-cell immune response and promote M2 macrophages, suppressing the antitumor immune response.

Research has revealed that RCC-derived EVs play a role in every step of metastasis, including cancer cell migration, invasion, and lung metastases through metastasis-associated lung adenocarcinoma transcript 1. They enhance the intravasation and extravasation of tumor cells by increasing vascular permeability. EVs from metastatic cancer cells and RCC stem cells also promote the microenvironment needed for metastasis formation.

Differences in EV cargo between drug-resistant and drug-sensitive cancer cells suggest that EVs might be involved in drug resistance. EVs from resistant cells contain biomolecules that contribute to cell survival and proliferation during anticancer drug treatments and transfer drug resistance from resistant to sensitive cells.

Potential Biomarkers for Renal Cell Carcinoma

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Several biomolecules packed into EVs are promising biomarker candidates for early RCC detection, predicting prognosis, and assessing response to treatment. Of particular interest is miRNA, which is higher in RCC patients than in healthy individuals and has been linked to progression-free and overall survival. Long non-coding RNA and mRNA have also been reported as potential candidates. Azurocidin and cavin-1, proteins abundant in RCC-derived EVs, also show potential as biomarkers. No EV-based biomarker has yet been implicated in clinical practice, and research is ongoing.

Advanced Drug Carriers in Cancer Therapy

EVs show potential as novel drug carriers due to their favorable biological properties, including efficient uptake by recipient cells and minimal immune reaction. Recent advances in nanotechnology allow for loading EVs with antitumor drugs, and research has shown substantial therapeutic effects in various studies. EVs obtained from immune cells also show promise as novel biological response modifiers and can stimulate the host immune response against tumor cells. However, for the clinical application of EV-based cancer therapy, it is essential to overcome the challenges of efficient EV production and cargo loading.    


Takeda, M., Akamatsu, S., Kita, Y., Goto, T., & Kobayashi, T. (2023). The Roles of Extracellular Vesicles in the Progression of Renal Cell Carcinoma and Their Potential for Future Clinical Application. Nanomaterials (Basel, Switzerland), 13(10). https://doi.org/10.3390/nano13101611