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A bioengineered metastatic pancreatic tumor model for mechanistic investigation of chemotherapeutic drugs

Wang, Xiaohui, Zhang, Xing, Fu, Zhiren, Yin, Hao
Journal of biotechnology 2013 v.166 pp. 166-173
apoptosis, biotechnology, carcinogenesis, drug therapy, drugs, gelatin, humans, metastasis, mice, microstructure, models, neoplasm cells, pancreas, pancreatic neoplasms, scientists, stem cells
Here we bioengineered a metastatic pancreatic tumor model with homogenous human CD133+CXCR4+ cancer stem cells (CSC) and a polyglyconate/gelatin electrospun scaffold. The scaffold sported a highly porous microstructure with the majority of fibers possessing a diameter between 500μm and 1500μm. The scaffold supported the growth of tumor cells without provoking apoptosis. The homogeneous CD133+CXCR4+ CSC was transplanted with the scaffold into the pancreas of nude mice to establish a metastatic pancreatic tumor. After 8 weeks, the tumor volume and weight in the scaffold model were 40.52% and 51.49% greater than the traditional model, respectively. The scaffold also increased the incidence of tumor formation and readily induced a hepatic metastasis. In this model we found that FOLFIRINOX possessed a superior capability of preventing the hepatic metastasis of pancreatic tumor cells than gemcitabine. A mechanistic study attributed this superiority to the fact that FOLFIRINOX could induce a greater apoptosis of CD133+CXCR4+ CSC, thus depriving the driving force of hepatic metastasis. This metastatic tumor model showed an increased incidence of tumor formation, an accelerated tumorigenesis and a significant hepatic metastasis, therefore offering scientists a proven platform to study chemotherapeutic drugs.