A 3-Dimensional Coculture Model to Visualize and Monitor Interaction Between Pancreatic Cancer and Islet ß Cells.

ABSTRACT

OBJECTIVES: To facilitate exploring a link between pancreatic ductal adenocarcinoma (PDAC) and diabetes mellitus, we constructed a novel 3-dimensional (3D) in vitro coculturing system for studying interactions between PDAC and islet cells. METHODS: Adopting a 3D rotary cell culture system, we have cocultured several PDAC cell lines and MIN6 islet ß cells. The cellular morphology and viability of both cell types were investigated by time-lapse imaging, confocal and scanning electron microscopy, and immunohistochemistry. RESULTS: The developed coculture method enabled the formation of 3D PDAC and ß-cell spheroids (pseudo islets). We showed that surface morphology and growth of cultured cells mimicked their in vivo appearance. In addition, the coculture demonstrated the affinity of the PDAC cells to grow around and invade the pseudo islets. CONCLUSIONS: Using rotary cell culture system, we have established a simple in vitro 3D pancreatic model. It is a flexible culture system that can easily be expanded with the addition of various stromal/neural components to further mimic in vivo conditions, thus enabling holistic investigation of the endocrine and exocrine pancreas.