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. 2025 Jul 24;15(16):8031–8048. doi: 10.7150/thno.115131

Figure 2.

Figure 2

Comparison of EVs derived from tumor cells and normal cells. Both types of EVs share a common bilayer membrane structure and carry proteins, lipids, and nucleic acids; however, their content and functions differ significantly. Tumor EVs are typically enriched in oncogenic proteins such as EGFR and HER2, tumor-promoting miRNAs including miR-21, immunosuppressive molecules (PD-L1), supporting cancer progression, angiogenesis, immune evasion, and metastasis. In contrast, EVs from healthy cells contain homeostatic markers (CD9, CD63, CD81, TSG101), functional mRNAs, and regulatory miRNAs, and they play roles in maintaining tissue equilibrium, intercellular communication, and immune surveillance. Tumor cells exhibit an increased rate of EV compared to normal cells, thereby amplifying their paracrine and systemic effects within the tumor microenvironment (TME). The TME is frequently characterized by hypoxic conditions, elevated levels of reactive oxygen species such as hydrogen peroxide, and metabolic stress, all of which influence the biogenesis, cargo composition, and functional impact of tumor-derived EVs. Importantly, tumor-derived EVs also interact dynamically with the extracellular matrix (ECM), contributing to its biochemical and biomechanical remodeling. The ECM often undergoes pathological stiffening due to aberrant deposition and cross-linking of matrix components such as collagen and fibronectin. Tumor EVs can exacerbate this process by delivering matrix-modifying enzymes and fibrogenic mediators, thereby facilitating ECM remodeling that supports tumor invasion, angiogenesis, and metastasis. Early endosome - EE, multivesicular body - MVB, intraluminal vesicles - ILV, major histocompatibility complex class I - MHCI, HSP - heat shock protein, Annexin A6+ - ANXA6, vascular endothelial growth factor - VEGF, platelet-derived growth factor - PDGF, fibroblast growth factor 2 - FGF2, tumor necrosis factor alpha - TNF-α, P-glycoprotein - P-gp, multidrug resistance protein 1 - MRP1, Tumor Susceptibility Gene 101 - TSG10, ALG-2-interacting protein X - ALIX. Created in https://BioRender.com.