In vivo and in vitro propagation of intraductal papillary mucinous neoplasms
| Autor: | Angela Young, Margaret Griffith, Anirban Maitra, Mihoko Kamiyama, Seung-Mo Hong, Hong Liang, Georg Feldmann, Chanjuan Shi, Collins Karikari, Masamichi Mizuma, Ralph H. Hruban, Alexis Norris-Kirby, Michael Goggins, James R. Eshleman, Michael Borges, Conrad Lubek, Hirohiko Kamiyama, Ming Tseh Lin |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Pathology endocrine system diseases pancreatic cancer precursor lesions Mice SCID Gene mutation medicine.disease_cause Mice 0302 clinical medicine Mice Inbred NOD CDKN2A Immunodeficient mice Aged 80 and over Mice Knockout Middle Aged Adenocarcinoma Mucinous Immunohistochemistry 3. Good health 030220 oncology & carcinogenesis Cell lines Female 030211 gastroenterology & hepatology Carcinoma Pancreatic Ductal Adult medicine.medical_specialty Transplantation Heterologous Mice Nude Biology Article Pathology and Forensic Medicine 03 medical and health sciences Cytokeratin In vivo Cell Line Tumor Pancreatic cancer medicine Animals Humans Molecular Biology Cyclin-Dependent Kinase Inhibitor p16 Aged Intraductal papillary mucinous neoplasm (IPMN) Cell Biology medicine.disease DNA Fingerprinting Carcinoma Papillary Pancreatic Neoplasms Cell culture Cancer research Carcinogenesis Neoplasm Transplantation |
| Zdroj: | Laboratory investigation; a journal of technical methods and pathology |
| ISSN: | 0023-6837 |
| DOI: | 10.1038/labinvest.2010.51 |
| Popis: | Background Intraductal papillary mucinous neoplasms (IPMNs) are one of the 3 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. Methods 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 fourteen cases by implanting them into nude, severe combined immunodeficient (SCID), and NOD/SCID/IL2Rγnull (NOG) mice, in addition to direct culture, to generate tumor xenografts and cell lines. One sample was directly cultured only. Results Thirteen tumors were implanted into the 3 types of mice, including 10 tumors implanted into the triple immunodeficient NOG mice, where the majority (8 of 10) grew. This included 5 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. Conclusions 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. |
| Databáze: | OpenAIRE |
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