In vivo and in vitro propagation of intraductal papillary mucinous neoplasms

Hirohiko Kamiyama, Mihoko Kamiyama, Seung Mo Hong, Collins A. Karikari, Ming Tseh Lin, Michael W. Borges, Margaret Griffith, Angela Young, Alexis Norris-Kirby, Conrad Lubek, Masamichi Mizuma, Georg Feldmann, Chanjuan Shi, Hong Liang, Michael G. Goggins, Anirban Maitra, Ralph H. Hruban, James R. Eshleman

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Intraductal papillary mucinous neoplasms (IPMNs) are one of the three known curable precursor lesions of invasive pancreatic ductal adenocarcinoma, an almost uniformly fatal disease. Cell lines from IPMNs and their invasive counterparts should be valuable to identify gene mutations critical to IPMN carcinogenesis, and permit high-throughput screening to identify drugs that cause regression of these lesions. To advance the study of the biological features of IPMNs, we attempted in vivo and in vitro growth of selected IPMNs based on the hypothesis that IPMNs could be grown in the most severely immunodeficient mice. We examined 14 cases by implanting them into nude, severe combined immunodeficient (SCID), and NOD/SCID/IL2Rγ null (NOG) mice, in addition to direct culture, to generate tumor xenografts and cell lines. One sample was directly cultured only. Thirteen tumors were implanted into the three types of mice, including 10 tumors implanted into the triple immunodeficient NOG mice, in which the majority (8 of 10) grew. This included five IPMNs lacking an invasive component. One of the explanted IPMNs, with an associated invasive carcinoma, was successfully established as a cell line. Tumorigenicity was confirmed by growth in soft agar, growth in immunodeficient mice, and the homozygous deletion of p16/cdkn2a. Epithelial differentiation of the cell line was documented by cytokeratin expression. Patient origin was confirmed using DNA fingerprinting. Most non-invasive IPMNs grow in NOG mice. We successfully established one IPMN cell line, and plan to use it to clarify the molecular pathogenesis of IPMNs.

Original languageEnglish
Pages (from-to)665-673
Number of pages9
JournalLaboratory Investigation
Volume90
Issue number5
DOIs
Publication statusPublished - 2010 May

Keywords

  • Cell lines
  • Immunodeficient mice
  • Intraductal papillary mucinous neoplasm (IPMN)
  • Pancreatic cancer
  • Precursor lesions

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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