Development of patient-derived xenograft models from a spontaneously immortal low-grade meningioma cell line, KCI-MENG1

作者: Sharon K Michelhaugh , Anthony R Guastella , Kaushik Varadarajan , Neil V Klinger , Prahlad Parajuli

DOI: 10.1186/S12967-015-0596-8

关键词: Clone (cell biology)Cell typeTelomerasePathologyMeningiomaBiologyBenign MeningiomaVimentinPsammoma bodyOlfactory Groove Meningioma

摘要: There is a paucity of effective therapies for recurrent/aggressive meningiomas. Establishment improved in vitro and vivo meningioma models will facilitate development testing novel therapeutic approaches. A primary cell line was generated from patient with an olfactory groove meningioma. The extensively characterized by performing analysis growth kinetics, immunocytochemistry, telomerase activity, karyotype, comparative genomic hybridization. Xenograft using immunocompromised SCID mice were also developed. Histopathology the tumor consistent WHO grade I typical composed meningothelial cells, whorls, occasional psammoma bodies. original early passage cells shared standard immunohistochemical profile low-grade, good prognosis Low KCI-MENG1 two types spindle round morphologies, showed linear curve, had very low distinct unrelated clones on cytogenetic analysis. In contrast, high homogeneously round, rapidly growing, single clone near triploid karyotype containing 64–66 chromosomes numerous aberrations. Following subcutaneous orthotopic transplantation into mice, firm tumors positive vimentin progesterone receptor (PR) formed, while implant yielded vimentin-positive, PR-negative tumors, concordant high-grade Although derived benign specimen, newly-established spontaneously immortal can be utilized to generate xenograft either low- or features, dependent number (likely due relative abundance near-triploid cells). These human mouse provide biologically relevant platforms which investigate differences vs. biology disease progression as well develop improve treatment options poor recurrent

参考文章(60)
Veerle L. Van Marck, Marc E. Bracke, Epithelial-Mesenchymal Transitions in Human Cancer Rise and fall of Epithelial Phenotype : concepts of Epithelial-Mesenchymal transition. pp. 135- 159 ,(2005) , 10.1007/0-387-28671-3_9
Katrin Lamszus, Meningioma Pathology, Genetics, and Biology Journal of Neuropathology and Experimental Neurology. ,vol. 63, pp. 275- 286 ,(2004) , 10.1093/JNEN/63.4.275
Katherine Striedinger, Scott R. VandenBerg, Gilson S. Baia, Michael W. McDermott, David H. Gutmann, Anita Lal, The neurofibromatosis 2 tumor suppressor gene product, Merlin, regulates human meningioma cell growth by signaling through YAP Neoplasia. ,vol. 10, pp. 1204- 1212 ,(2008) , 10.1593/NEO.08642
Timothy W. Dziuk, Shiao Woo, E. Brian Butler, Jack Thornby, Robert Grossman, W. Sam Dennis, Hsin Lu, L. Steven Carpenter, J. Kam Chiu, Malignant meningioma: an indication for initial aggressive surgery and adjuvant radiotherapy. Journal of Neuro-oncology. ,vol. 37, pp. 177- 188 ,(1998) , 10.1023/A:1005853720926
M. Jansen, G. Mohapatra, R. A. Betensky, C. Keohane, D. N. Louis, Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression‐free survival Neuropathology and Applied Neurobiology. ,vol. 38, pp. 213- 219 ,(2012) , 10.1111/J.1365-2990.2011.01222.X
David N. Louis, WHO classification of tumours of the central nervous system International Agency for Research on Cancer. ,(2007)
Arie Perry, Bernd W. Scheithauer, Scott L. Stafford, Christine M. Lohse, Peter C. Wollan, "Malignancy" in meningiomas: a clinicopathologic study of 116 patients, with grading implications. Cancer. ,vol. 85, pp. 2046- 2056 ,(1999) , 10.1002/(SICI)1097-0142(19990501)85:9<2046::AID-CNCR23>3.0.CO;2-M
Stéphane Goutagny, Jean C. Nault, Maxime Mallet, Dominique Henin, Jessica Z. Rossi, Michel Kalamarides, High incidence of activating TERT promoter mutations in meningiomas undergoing malignant progression. Brain Pathology. ,vol. 24, pp. 184- 189 ,(2014) , 10.1111/BPA.12110
Brian J. Goldsmith, William M. Wara, Charles B. Wilson, David A. Larson, Postoperative irradiation for subtotally resected meningiomas: A retrospective analysis of 140 patients treated from 1967 to 1990 Journal of Neurosurgery. ,vol. 80, pp. 195- 201 ,(1994) , 10.3171/JNS.1994.80.2.0195