Effects of glucose starvation on proteomic profiling of gastric cancer cell-derived exosomes cultured in 3D hydrogel

Abstract

Since the importance of exosomes which are one of the tools of cell-cell communication in the tumor microenvironment has emerged, many studies on exosomes have been conducted. It is known that there is a gradient of nutrients such as glucose depending on the distance from blood vessels in the tumor microenvironment. Recently, a glucose gradient was confirmed in gastric cancer tissue, and it was revealed that specific metabolic activities exist for each cell at each location in the tumor tissue. Research is needed because exosomes, one of the important mediators in cell-cell communication, can be involved in these metabolic activities. However, exosomes obtained through conventional two-dimensional cell culture are different from exosomes in actual blood exosomes, so a new in vitro model is needed. In this thesis, proteomic analysis was performed on gastric cancer cell-derived exosomes grown in a three-dimensional collagen hydrogel depicting the glucose concentration gradient and extracellular matrix in the tumor microenvironment. It was confirmed that the protein composition of exosomes secreted by gastric cancer cells grown in environments with different glucose concentrations was changed, and the effect of 3D cell culture was also confirmed. Biomarkers of each exosome were found through proteomic analysis of exosomes obtained in each glucose concentration environment. The exosome-derived biomarkers obtained in this way can be used as indicators to detect changes in the tumor microenvironment of actual gastric cancer patients.