Mucinous cystic carcinoma of the pancreas: a inique 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.