Paper-supported co-culture system for dynamic investigating the lung-tropic migration of breast cancer cells.

Tumor tropism metastasis is a multi-step process that involves the interactions between tumor cells and microenvironment. Due to the limitations of experimental techniques, the current studies are not able to gain insight into the dynamic process of such tropism migration. To overcome this issue, we developed a paper-supported co-culture system for dynamic investigating the lung-tropic migration of breast cancer cells. This co-culture system contains a tumor layer, a recruitment layer, and several invasion layers between these two parts. The tumor layer and the recruitment layer are impregnated with breast cancer cells and lung cells, respectively. Stacking these layers forms a co-culture device that comprises interactions between breast cancer and lung, destacking such a device represents cancer cells at different stages of the migration process. Thus, the paper-supported co-culture system offers the possibility of investigating migration from temporal and spatial aspects. Invasion assays using the co-culture system showed that breast cancer cells induced lung fibroblasts to convert to cancer associate fibroblasts (CAFs), and the CAFs, in turn, recruited breast cancer cells. During migration, the local invasion of the cancer cells is a collective behavior, while the long-distance migration comes from individual cell behaviors. Breast cancer cells experienced repetitive processes of migration and propagation, accompanied by epithelial-mesenchymal and mesenchymal-epithelial transitions, and changes in stemness and drug resistance. Based on these results, the lung-tropic migration of breast cancer is interpreted as a process of bilateral interaction with the local and the host-organ microenvironment. The developed paper-supported co-culture system offers the possibility of dynamic investigating tropism migration under the pre-metastatic niche, thus providing an advantageous tool for studying tumor metastasis.