Biomaterial Substrate-derived Compact Cellular Spheroids Mimicking Pancreatic Cancer Microenvironment
09:50 - 10:10, Room 104 (104講堂)
Biomaterial substrate-derived compact cellular spheroids mimicking pancreatic cancer microenvironment
Pancreatic stromal cells especially pancreatic stellate cells (PSCs) play a critical role in the progression of human pancreatic ductal adenocarcinoma (PDAC). The exact interaction between cancer cells and PSCs remains to be elucidated in order to develop more effective therapeutic approaches to treat PDAC. The microenvironment of PDAC shows higher hyaluronan (HA) levels, which is associated with poor prognosis of PDAC patients. We developed an efficient three-dimensional tumor spheroid model for PDAC, where the pancreatic cancer cells and PSCs were co-cultured on hyaluronan grafted chitosan (CS-HA) coated plates to generate 3D tumor-like co-spheroids. These spheroids displayed potent in vitro tumorigenicity such as up-regulated expression of stemness and migration markers. The migration rate of cancer cells in spheroids was also enhanced. This unique co-spheroidal structure with the outer wrap of PSCs contributed to the chemo-resistance of pancreatic cancer cells to gemcitabine as well as sensitivity to the combined gemcitabine and Abraxane treatment in vitro. The metastatic nature of the spheroids was confirmed by the zebrafish xenograft model in vivo. The compact and dynamic pancreatic cancer-PSC co-spheroids generated by the unique 3D co-culture platform on CS-HA biomaterials mimic the PSC-constituting microenvironment of PDAC and have potential applications in personalized and high-throughput drug screening. Refinement of the model by more cell types is under investigation.