Nanomechanical Analysis of Living Small Extracellular Vesicles to Identify Gastric Cancer Cell Malignancy Based on a Biomimetic Peritoneum.

Abstract

Gastric cancer is one of the most prevalent digestive malignancies. The lack of effective in vitro peritoneal models has hindered the exploration of the potential mechanisms behind gastric cancer's peritoneal metastasis. An accumulating body of research indicates that small extracellular vesicles (sEVs) play an indispensable role in peritoneal metastasis of gastric cancer cells. In this study, a biomimetic peritoneum was constructed. The biomimetic model is similar to real peritoneum in internal microstructure, composition, and primary function, and it enables the recurrence of peritoneal metastasis process in vitro. Based on this model, the association between the mechanical properties of sEVs and the invasiveness of gastric cancer was identified. By performing nanomechanical analysis on sEVs, we found that the Young's modulus of sEVs can be utilized to differentiate between malignant clinical samples (ascites) and nonmalignant clinical samples (peritoneal lavage). Furthermore, patients' ascites-derived sEVs were verified to stimulate the mesothelial-to-mesenchymal transition, thereby promoting peritoneal metastasis. In summary, nanomechanical analysis of living sEVs could be utilized for the noninvasive diagnosis of malignant degree and peritoneal metastasis of gastric cancer. This finding is expected to contribute future treatments.