Establishment and characterization of a highly tumourigenic and cancer stem cell enriched pancreatic cancer cell line as a well defined model system

Standard cancer cell lines do not model the intratumoural heterogeneity situation sufficiently. Clonal selection leads to a homogeneous population of cells by genetic drift. Heterogeneity of tumour cells, however, is particularly critical for therapeutically relevant studies, since it is a prerequis...

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Auteurs principaux: Fredebohm, Johannes (Auteur) , Gaida, Matthias (Auteur) , Heller, Anette (Auteur) , Keleg, Shereen (Auteur) , Giese, Nathalia (Auteur)
Format: Article (Journal)
Langue:anglais
Publié: November 12, 2012
In: PLOS ONE
Year: 2012, Volume: 7, Numéro: 11
ISSN:1932-6203
DOI:10.1371/journal.pone.0048503
Accès en ligne:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1371/journal.pone.0048503
Verlag, kostenfrei, Volltext: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0048503
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Notes sur l'auteur:Johannes Fredebohm, Michael Boettcher, Christian Eisen, Matthias M. Gaida, Anette Heller, Shereen Keleg, Jörg Tost, Karin M. Greulich-Bode, Agnes Hotz-Wagenblatt, Mark Lathrop, Nathalia A. Giese, Jörg D. Hoheisel
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Résumé:Standard cancer cell lines do not model the intratumoural heterogeneity situation sufficiently. Clonal selection leads to a homogeneous population of cells by genetic drift. Heterogeneity of tumour cells, however, is particularly critical for therapeutically relevant studies, since it is a prerequisite for acquiring drug resistance and reoccurrence of tumours. Here, we report the isolation of a highly tumourigenic primary pancreatic cancer cell line, called JoPaca-1 and its detailed characterization at multiple levels. Implantation of as few as 100 JoPaca-1 cells into immunodeficient mice gave rise to tumours that were histologically very similar to the primary tumour. The high heterogeneity of JoPaca-1 was reflected by diverse cell morphology and a substantial number of chromosomal aberrations. Comparative whole-genome sequencing of JoPaca-1 and BxPC-3 revealed mutations in genes frequently altered in pancreatic cancer. Exceptionally high expression of cancer stem cell markers and a high clonogenic potential in vitro and in vivo was observed. All of these attributes make this cell line an extremely valuable model to study the biology of and pharmaceutical effects on pancreatic cancer.
Description:Gesehen am 27.04.2018
Description matérielle:Online Resource
ISSN:1932-6203
DOI:10.1371/journal.pone.0048503