title: A novel cell line and xenograft model of ampulla of Vater adenocarcinoma.
abstract: Ampulla of Vater cancers (AVC) are of clinical relevance, as they represent more than one-third of patients undergoing surgery for pancreaticoduodenal malignancies and have a better prognosis than periampullary cancers of pancreaticobiliary origin. The availability of cellular models is crucial to perform cell biology and pharmacological studies and clarify the relationship between AVC and pancreatic and biliary cancers. Numerous cell lines are available for pancreatic and biliary adenocarcinomas, while only two have been reported recently for AVC. These were derived from a poor and a well-differentiated AVC, and both had wild-type K- ras and mutated p53. We report the establishment of a novel AVC cell line (AVC1) derived from a moderately differentiated cancer, having a mutated K- ras, wild-type p53, and methylated p16. Thus, our cell line adds to the spectrum of available in vitro models representative of the different morphological and molecular presentations of primary AVC. We further characterized AVC1 for the expression of relevant cell surface molecules and sensitivity to chemotherapeutic agents of common clinical use. It expresses MHC-I and CD95/Fas, while HLA-DR, CD40, CD80, CD86, MUC-1, MUC-2, and ICAM-1/CD54 are absent. It has a low to moderate sensitivity to both 5-FU and gemcitabine, at variance with much higher sensitivity displayed by two pancreatic ductal carcinoma cell lines. Lastly, AVC1 can be readily xenografted in immunodeficient mice, making it a suitable model for pre-clinical studies.
authors.affiliation: Dipartimento di Patologia, Università di Verona, Strada Le Grazie, 37134, Verona, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Sorio
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Moore
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Ennas
authors.forename: Cristina
authors.initials: C
authors.lastname: Tecchio
authors.forename: Antonio
authors.initials: A
authors.lastname: Bonora
authors.forename: Silvia
authors.initials: S
authors.lastname: Sartoris
authors.forename: Piera
authors.initials: P
authors.lastname: Balzarini
authors.forename: Piergiovanni
authors.initials: P
authors.lastname: Grigolato
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D014670:Ampulla of Vater; D000818:Animals; D002448:Cell Adhesion; D003138:Common Bile Duct Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005472:Fluorouracil / Q000627:therapeutic use; D019942:Genes, p16; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology; D007621:Karyotyping; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009368:Neoplasm Transplantation; D011003:Ploidies; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D007371:Interferon-gamma; D005472:Fluorouracil; D000093542:Gemcitabine