Mucinous cystic carcinoma of the pancreas: a unique cell line and xenograft model of a preinvasive lesion.
Pancreatic mucinous cystic tumors (MCT) are proliferations of mucin-producing epithelia supported by an ovarian-like stroma. They are classified into adenomas (MCA), borderline (MCB) and noninvasive or invasive carcinomas (MCC). The molecular mechanisms underlying their clinical behavior are poorly understood, partly due to the lack of cellular models. We report the establishment of MCC1, the first cell line from a pancreatic MCT, deriving from the highly dysplastic cell component of a noninvasive MCC. MCC1 has mutations in codon 12 of K-RAS (GGT>GAT), codon 58 of P16 (CGA>TGA) and codon 132 of P53 (AAG>AGG). The FHIT and DPC4 genes are unaltered. Immunohistochemistry shows abnormal expression of MUC1 and p53, loss of p16 and retention of Fhit and Dpc4 in both the cell line and the highly dysplastic cells of the primary lesion. The morphological and molecular features of MCC1 and its corresponding primary tumor are consistent with a model for non-invasive MCC, where K-RAS, P16, P53 and MUC1 alterations are pre-invasive changes associated with progression of malignancy of MCT from adenoma to carcinoma. MCC1 is sensitive to 5-fluorouracil, representing the first assessment of drug sensitivity for MCC. Finally, MCC1 is a suitable model for preclinical studies, as it grows in immunodeficient mice.
Sorio
Claudio
C
Dipartimento di Patologia, Università di Verona, Strada Le Grazie 8, 37134 Verona, Italy.
Capelli
Paola
P
Lissandrini
Daniele
D
Moore
Patrick S
PS
Balzarini
Piera
P
Falconi
Massimo
M
Zamboni
Giuseppe
G
Scarpa
Aldo
A
D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018282:Cystadenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D005472:Fluorouracil