(193h) Construction of a Multi-Culture Human Lung Platform for Tumor Metastasis Study

Lung cancer is one of the most common malignancies and the leading causes of cancer-related death in the world. Many clinical data has shown cancer metastasis is the major reason that causes the death of patients. To investigate the mechanism of metastasis, reconstruction of tumor microenvironment in vitro is considered as an easily accessible approach that can mimic the complex and multiple interactions between lung tumor cells and other surrounding tissue. However, the existing devices usually involve two or three types of cell co-culture together which are not able to represent the complex tumor microenvironment. Here we developed a microfluidic-based platform that can culture lung cancer cells, epithelial cells, fibroblasts and muscle cells in the same format.

Studies are aimed at understanding if the invasion mechanism of carcinoma cells can be regulated by the surrounded stromal cells. We have developed a technique to fabricate a microfluidic device that contains five of cell culture chambers. The cells in each chamber can grow in their own medium and share the same flow system that simulates the microvasculature. The culture chamber for each cell line was spatially separated by the embedded -hydrogel in the microfluidic channels so that the migration results of cancer cells can be dynamically and quantitatively obtained. We found that when the cancer cells were cultured surrounded by other stromal cells, the migration of cancer cells can be regulated. For example, epithelial cells started to lose their characteristic proteins which indicated that the epithelial–mesenchymal transition (EMT) might occur in the tumor microenvironment. Furthermore, the fibroblasts were activated into myofibroblast by cancer cells. These changes also increased the stiffness of hydrogel surrounding cancer cells and improved the migration ability of cancer cells. Taken together our results showed that with the existing stromal cells, the multiple interactions within the microenvironment could further enhance the migration of cancer cells compared to the culture with a single type of cells. By cultivating other cell types, this dynamic tumor culture platform could be served as an in vitro model to study initiation, progression, and remediation of cancers.