(A) study on spatial restriction by extracellular matrix initiating gastric cancer progression through promotion of epithelial mesenchymal transition

Abstract

Epithelial-mesenchymal transition is an important feature in epithelial carcinomas during invasion and metastasis into neighboring tissues and vasculatures. It is well known that various cues trigger EMT in tumors, but the role of spatial confinement as a mechano-physical EMT trigger has not yet been fully examined. In this thesis, a collagen hydrogel sandwich platform is used to provide physical constraint to the growth of gastric cancer cells. Upon spatial restriction, GC cells formed cluster morphology and proliferated vertically. Matrix adhesion proteins and mesenchymal marker expressions were also elevated. Finally, YAP was localized to the nucleus and transcriptionally active under spatial restriction. These results indicate that spatial restraint is an effective tool to induce EMT in gastric epithelial carcinomas and suggests that targeting the microenvironment to relieve mechanical stress may be desirable in cancer therapy.