Probing tumor microtissue formation and epithelial-mesenchymal transition on a well-mesh microchip.

Abstract

Three-dimensional cultures of tumor microtissues and biomimetic simulation of tumor microenvironments are of great significance in the study of tumorigenesis and development processes. In this study, a well-mesh microchip was developed to realize the formation and culture of tumor microtissues in vitro. Human lung adenocarcinoma HCC827 cells and large-cell lung cancer NCI-H460 cells were used. The size and morphology of the microtissues have been observed. In addition, we constructed an in situ three-dimensional co-culture model with tumor cell microtissues (HCC827 or NCI-H460 cells), extracellular matrix (Matrigel), and human umbilical vein endothelial cells. HCC827 microtissue epithelial-mesenchymal transition (EMT) in the established well-mesh microchip also was investigated, and the results showed that recombinant transforming growth factor could activate the Snail and Akt gene and promote migration and EMT with the decrease of E-cadherin expression for HCC827. This well-mesh microchip features simple operation and easy observation, and could provide a new method for the study of tumor cells and tumor microenvironments in vitro. Therefore, this model has potential application value in organ-on-chip technology, tissue engineering, and drug evaluation.