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 wildtype 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 Kras, 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.

A novel cell line and xenograft model of ampulla of Vater adenocarcinoma

ENNAS, MARIA GRAZIA;
2004

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 wildtype 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 Kras, 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.
Periampullary cancer; Cell line; Ampulla of Vater
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/12652
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 7
social impact