Effects of Glucose Concentration on the Cargo Profile of Gastric Cancer Cell-Derived Extracellular Vesicles

ABSTRACT: Extracellular vesicles (EVs) play a pivotal role in mediating intercellular communication within the tumor microenvironment, particularly by transferring bioactive molecules such as proteins, RNAs, and lipids. Emerging evidence suggests that the metabolic state of cancer cells can influence the composition and function of their secreted EVs, thereby modulating tumor progression and stromal reprogramming. However, the extent to which glucose availability shapes the cargo profile of EVs in gastric cancer (GC) remains poorly understood. To address this question, we cultured GAN-KP gastric cancer cells under three glucose conditions—normal glucose (LG, physiological level), high glucose (HG), and long-term high glucose (LHG, simulating chronic diabetic conditions)—and subsequently isolated EVs from the conditioned media. Proteomic and transcriptomic profiling of EV cargo revealed marked differences among the three groups, suggesting a glucose-dependent reprogramming of EV content. Notably, comparative analysis identified 44 genes that were consistently upregulated in EVs from both HG and LHG conditions compared to LG. These genes are potentially involved in extracellular matrix organization, immune modulation, and fibroblast activation. The findings indicate that elevated glucose levels not only affect cancer cell-intrinsic signaling but also alter the communicative potential of tumor-derived EVs, possibly contributing to the formation of a pro-metastatic niche. Functional validation of key EV cargo molecules is currently underway to elucidate their roles in stromal remodeling and metastasis facilitation.

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Takatsugu Ishimoto 

PROVIDER: PXD066305 | JPOST Repository | Sat Jul 18 00:00:00 BST 2026

REPOSITORIES: jPOST