title: A bioengineered metastatic pancreatic tumor model for mechanistic investigation of chemotherapeutic drugs.
abstract: 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.
authors.affiliation: Department of General Surgery, Bayinguoleng Menggu Zizhizhou People's Hospital, Korla, Xinjiang, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhiren
authors.initials: Z
authors.lastname: Fu
authors.forename: Hao
authors.initials: H
authors.lastname: Yin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D057005:Bioengineering / Q000379:methods*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D054457:Tissue Scaffolds; D023041:Xenograft Model Antitumor Assays / Q000295:instrumentation / Q000379:methods*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D003841:Deoxycytidine; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin; D000093542:Gemcitabine
keywords: Chemotherapy; Electrospun scaffold; Metastasis; Orthotopic model; Pancreatic cancer