Extracellular vesicles (EVs) are a heterogeneous collection of membrane-bound structures that play key roles in intercellular communication. EVs are potent regulators of tumorigenesis and function largely via the shuttling of cargo molecules (RNA, DNA, protein, etc.) among cancer cells and the cells of the tumor stroma. EV-based crosstalk can promote proliferation, shape the tumor microenvironment, enhance metastasis, and allow tumor cells to evade immune destruction. In many cases these functions have been linked to the presence of specific cargo molecules. Herein we will review various types of EV cargo molecule and their functional impacts in the context of oncology.

Cervical cancer remains a significant global health challenge, particularly in its advanced stages, where treatment resistance complicates effective management. Extracellular vesicles (EVs) are crucial mediators of tumor progression and resistance, primarily through the transfer of miRNA cargo. In cervical cancer, specific miRNAs, including oncogenic miRNAs such as miR-21, miR-221-3p, miR-486-5p, and miR-92a-3p are upregulated in both cells and EVs, promoting proliferation, migration, epithelial-to-mesenchymal transition (EMT), and immune evasion-all of which contribute to therapy resistance and an aggressive tumor phenotype. Conversely, tumor-suppressive miRNAs, such as miR-122-5p, miR-100, and miR-142-3p, are selectively exported from cancer cells via EVs, suggesting a protective mechanism by which cancer cells eliminate these tumor suppressors. This review focuses on the role of oncogenic and tumor-suppressive miRNAs within EVs and their implications for cervical cancer progression and treatment resistance. Additionally, it examines the dynamic interactions between the tumor microenvironment (TME) and EV cargo, as well as emerging EV-based therapeutic strategies. These include the encapsulation of chemotherapeutic agents within EVs, the use of anti-miRs to silence oncogenic miRNAs, the delivery of tumor-suppressive miRNAs, the inhibition of EV release, and the targeting of downstream miRNA-regulated proteins. While miRNA-based therapies remain in the early stages, they hold significant promise for overcoming treatment resistance and improving cervical cancer outcomes.

Background: Lung cancer, including the major subtype lung adenocarcinoma (LUAD), is the leading cause of cancer deaths worldwide, largely due to metastasis. Improving survival rates requires new treatment strategies and a deeper understanding of the mechanisms that drive tumor progression within the tumor microenvironment (TME). This study investigated the impact of extracellular vesicles (EVs) derived from LUAD cells on lung fibroblasts. Methods: EVs were isolated from LUAD cell lines via ultracentrifugation and characterized using nanoparticle tracking analysis and Western blotting. Lung fibroblasts were treated with PBS, TGFβ, or EVs, and their activation was assessed through protein (Western blotting) and RNA analyses (RNA seq and RT-qPCR). Results: The results confirmed the TGFβ induced activation and showed that LUAD EVs could also activate fibroblasts, increasing cancer-associated fibroblast (CAF) markers. While EV-induced CAF activation displayed unique features, like an increase in proliferation-related genes, the EV and TGFβ treatments also shared some differentially expressed genes. The EV groups induced a higher expression of ECM remodeling and EMT-associated genes, but some of those genes were also upregulated in the TGFβ group. Mesenchymal genes POSTN and SPOCK1 were significantly upregulated in TGFβ- and EV-treated fibroblasts. Their secretion as proteins from the TGFβ- and EV-induced CAFs was not significant, confirmed through ELISA. Conclusions: These findings suggest that LUAD EVs play a role in CAF activation through both shared and distinct pathways compared to canonical TGFβ activation, potentially identifying novel gene expressions involved in CAF activation. Additionally, optimal protein secretion conditions of confirmed CAF-upregulated genes need to be established to determine their contribution to the TME.