TY - JOUR
T1 - In vivo and in vitro propagation of intraductal papillary mucinous neoplasms
AU - Kamiyama, Hirohiko
AU - Kamiyama, Mihoko
AU - Hong, Seung Mo
AU - Karikari, Collins A.
AU - Lin, Ming Tseh
AU - Borges, Michael W.
AU - Griffith, Margaret
AU - Young, Angela
AU - Norris-Kirby, Alexis
AU - Lubek, Conrad
AU - Mizuma, Masamichi
AU - Feldmann, Georg
AU - Shi, Chanjuan
AU - Liang, Hong
AU - Goggins, Michael G.
AU - Maitra, Anirban
AU - Hruban, Ralph H.
AU - Eshleman, James R.
N1 - Funding Information:
We acknowledge Dr Ming Tsao for generously providing the HPDE cell line. We also acknowledge Drs Elizabeth M Jaffee, Robert Anders, and Rajni Sharma for helpful discussions, in addition to Ms Guanglan Mo and Dante Trusty for helpful discussions and technical support. This work was funded, in part, by RO1CA130938 (JRE) and P50CA62924 (PI: Dr Scott Kern), the Stewart Trust, the Michael Rolfe Pancreatic Cancer Foundation, and the Mary Lou Wootton Pancreatic Cancer Research Fund.
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
KW - Cell lines
KW - Immunodeficient mice
KW - Intraductal papillary mucinous neoplasm (IPMN)
KW - Pancreatic cancer
KW - Precursor lesions
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U2 - 10.1038/labinvest.2010.51
DO - 10.1038/labinvest.2010.51
M3 - Article
C2 - 20231822
AN - SCOPUS:77951782062
SN - 0023-6837
VL - 90
SP - 665
EP - 673
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 5
ER -