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: Claudio Sorio, Patrick S Moore, Maria Grazia Ennas, Cristina Tecchio, Antonio Bonora, Silvia Sartoris, Piera Balzarini, Piergiovanni Grigolato, Aldo Scarpa
• Journal: Virchows Archiv : an international journal of pathology (Virchows Arch) Vol. 444 Issue 3 Pg. 269-77 (Mar 2004) ISSN: 0945-6317 [Print] Germany
• PMID: 14677066 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Deoxycytidine
• Interferon-gamma
• Fluorouracil
• Gemcitabine

Topics

• Adenocarcinoma (drug therapy, genetics, pathology)
• Ampulla of Vater
• Animals
• Cell Adhesion
• Common Bile Duct Neoplasms (drug therapy, genetics, pathology)
• DNA Methylation
• Deoxycytidine (analogs & derivatives, therapeutic use)
• Fluorouracil (therapeutic use)
• Genes, p16
• Genes, p53 (genetics)
• Genes, ras (genetics)
• Humans
• Immunophenotyping
• Interferon-gamma (pharmacology)
• Karyotyping
• Mice
• Mice, Nude
• Mutation
• Neoplasm Transplantation
• Ploidies
• Transplantation, Heterologous
• Tumor Cells, Cultured
• Gemcitabine