Novel xenograft and cell line derived from an invasive intraductal papillary mucinous neoplasm of the pancreas give new insights into molecular mechanisms

Stefan Fritz, Carlos Fernández-Del Castillo, A. John Iafrate, Mari Mino-Kenudson, Nancy Neyhard, Jennifer Lafemina, Amy Stirman, Andrew L. Warshaw, Sarah P Thayer

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objectives: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are a unique entity with malignant potential. Histologically, pancreatic ductal adenocarcinoma (PDAC) arising in IPMN (intraductal papillary mucinous carcinoma [IPMC]) appears similar to sporadic PDAC; biologically, however, IPMC seems to have a less aggressive clinical course. Little is known about the genetic signature of IPMC. In this study, we describe a novel xenograft model and cell culture created to biologically and genetically characterize these tumors. Methods: Xenograft mice and cell lines were created from IPMC. Global genomic changes were evaluated by cytogenetic analysis and array comparative genomic hybridization. Specific mutations and sonic hedgehog (Shh) pathway activity were examined and xenografts evaluated for sensitivity to anti-Shh therapy. Results: Cytogenetic analysis showed a tetraploid karyotype with multiple aberrations. KRAS and p53 mutations and overexpression of the Shh pathway were identified. Array comparative genomic hybridization revealed multiple chromosomal aberrations comparable with previously published data in IPMNs. Murine xenograft tumors were sensitive to anti-Shh treatment. Conclusions: Characterization of IPMC cell lines and xenografts reveals similarities to previously published data on IPMN. In comparison to PDAC, moreover, these data reveal shared aberrations and distinct genomic changes. Thus, these xenograft model and cell lines may be useful for future preclinical investigations.

Original languageEnglish (US)
Pages (from-to)308-314
Number of pages7
JournalPancreas
Volume39
Issue number3
DOIs
StatePublished - Apr 1 2010

Fingerprint

Mucinous Adenocarcinoma
Carcinoma, Intraductal, Noninfiltrating
Pancreatic Neoplasms
Heterografts
Papillary Carcinoma
Hedgehogs
Cell Line
Adenocarcinoma
Comparative Genomic Hybridization
Cytogenetic Analysis
Neoplasms
Mutation
Tetraploidy
Karyotype
Chromosome Aberrations
Cell Culture Techniques

Keywords

  • Cell line
  • Genetic characterization
  • Intraductal papillary mucinous neoplasms
  • Pancreas
  • Xenograft

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Cite this

Novel xenograft and cell line derived from an invasive intraductal papillary mucinous neoplasm of the pancreas give new insights into molecular mechanisms. / Fritz, Stefan; Fernández-Del Castillo, Carlos; Iafrate, A. John; Mino-Kenudson, Mari; Neyhard, Nancy; Lafemina, Jennifer; Stirman, Amy; Warshaw, Andrew L.; Thayer, Sarah P.

In: Pancreas, Vol. 39, No. 3, 01.04.2010, p. 308-314.

Research output: Contribution to journalArticle

Fritz, S, Fernández-Del Castillo, C, Iafrate, AJ, Mino-Kenudson, M, Neyhard, N, Lafemina, J, Stirman, A, Warshaw, AL & Thayer, SP 2010, 'Novel xenograft and cell line derived from an invasive intraductal papillary mucinous neoplasm of the pancreas give new insights into molecular mechanisms', Pancreas, vol. 39, no. 3, pp. 308-314. https://doi.org/10.1097/MPA.0b013e3181bd5c10
Fritz, Stefan ; Fernández-Del Castillo, Carlos ; Iafrate, A. John ; Mino-Kenudson, Mari ; Neyhard, Nancy ; Lafemina, Jennifer ; Stirman, Amy ; Warshaw, Andrew L. ; Thayer, Sarah P. / Novel xenograft and cell line derived from an invasive intraductal papillary mucinous neoplasm of the pancreas give new insights into molecular mechanisms. In: Pancreas. 2010 ; Vol. 39, No. 3. pp. 308-314.
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AB - Objectives: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are a unique entity with malignant potential. Histologically, pancreatic ductal adenocarcinoma (PDAC) arising in IPMN (intraductal papillary mucinous carcinoma [IPMC]) appears similar to sporadic PDAC; biologically, however, IPMC seems to have a less aggressive clinical course. Little is known about the genetic signature of IPMC. In this study, we describe a novel xenograft model and cell culture created to biologically and genetically characterize these tumors. Methods: Xenograft mice and cell lines were created from IPMC. Global genomic changes were evaluated by cytogenetic analysis and array comparative genomic hybridization. Specific mutations and sonic hedgehog (Shh) pathway activity were examined and xenografts evaluated for sensitivity to anti-Shh therapy. Results: Cytogenetic analysis showed a tetraploid karyotype with multiple aberrations. KRAS and p53 mutations and overexpression of the Shh pathway were identified. Array comparative genomic hybridization revealed multiple chromosomal aberrations comparable with previously published data in IPMNs. Murine xenograft tumors were sensitive to anti-Shh treatment. Conclusions: Characterization of IPMC cell lines and xenografts reveals similarities to previously published data on IPMN. In comparison to PDAC, moreover, these data reveal shared aberrations and distinct genomic changes. Thus, these xenograft model and cell lines may be useful for future preclinical investigations.

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