Establishment and Characterization of a Highly Tumourigenic and Cancer Stem Cell Enriched Pancreatic Cancer Cell Line as a Well Defined Model System

被引：34

作者：

Fredebohm, Johannes ^{[1
]}

Boettcher, Michael ^{[1
]}

Eisen, Christian ^{[1
]}

Gaida, Matthias M. ^{[2
]}

Heller, Anette ^{[3
]}

Keleg, Shereen ^{[3
]}

Tost, Joerg ^{[4
]}

Greulich-Bode, Karin M. ^{[1
]}

Hotz-Wagenblatt, Agnes ^{[1
]}

Lathrop, Mark ^{[4
]}

Giese, Nathalia A. ^{[3
]}

Hoheisel, Joerg D. ^{[1
]}

机构：

[1] German Canc Res Ctr, Heidelberg, Germany

[2] Univ Heidelberg Hosp, Inst Pathol, Heidelberg, Germany

[3] Univ Heidelberg Hosp, European Pancreas Ctr, Heidelberg, Germany

[4] Ctr Natl Genotypage, Inst Genom, Evry, France

来源：

PLOS ONE | 2012年 / 7卷 / 11期

关键词：

GENOME-WIDE ASSOCIATION; DUCTAL ADENOCARCINOMAS; EPITHELIAL-CELLS; INVASION; MARKER; GENE; GEMCITABINE; EXPRESSION; MUTATIONS; VARIANTS;

D O I：

10.1371/journal.pone.0048503

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

共 80 条

[1] Immunoassay-based proteome profiling of 24 pancreatic cancer cell lines [J].

Alhamdani, Mohamed Saiel Saeed ;

Youns, Mahmoud ;

Buchholz, Malte ;

Gress, Thomas M. ;

Beckers, Marie-Claire ;

Marechal, Daniel ;

Bauer, Andrea ;

Schroeder, Christoph ;

Hoheisel, Joerg D. .

JOURNAL OF PROTEOMICS, 2012, 75 (12) :3747-3759

[2] Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer [J].

Amundadottir, Laufey ;

Kraft, Peter ;

Stolzenberg-Solomon, Rachael Z. ;

Fuchs, Charles S. ;

Petersen, Gloria M. ;

Arslan, Alan A. ;

Bueno-de-Mesquita, H. Bas ;

Gross, Myron ;

Helzlsouer, Kathy ;

Jacobs, Eric J. ;

LaCroix, Andrea ;

Zheng, Wei ;

Albanes, Demetrius ;

Bamlet, William ;

Berg, Christine D. ;

Berrino, Franco ;

Bingham, Sheila ;

Buring, Julie E. ;

Bracci, Paige M. ;

Canzian, Federico ;

Clavel-Chapelon, Francoise ;

Clipp, Sandra ;

Cotterchio, Michelle ;

de Andrade, Mariza ;

Duell, Eric J. ;

Fox, John W., Jr. ;

Gallinger, Steven ;

Gaziano, J. Michael ;

Giovannucci, Edward L. ;

Goggins, Michael ;

Gonzalez, Carlos A. ;

Hallmans, Goran ;

Hankinson, Susan E. ;

Hassan, Manal ;

Holly, Elizabeth A. ;

Hunter, David J. ;

Hutchinson, Amy ;

Jackson, Rebecca ;

Jacobs, Kevin B. ;

Jenab, Mazda ;

Kaaks, Rudolf ;

Klein, Alison P. ;

Kooperberg, Charles ;

Kurtz, Robert C. ;

Li, Donghui ;

Lynch, Shannon M. ;

Mandelson, Margaret ;

McWilliams, Robert R. ;

Mendelsohn, Julie B. ;

Michaud, Dominique S. .

NATURE GENETICS, 2009, 41 (09) :986-U47

[3]

Argani P, 2001, CLIN CANCER RES, V7, P3862

[4] The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website [J].

Bamford, S ;

Dawson, E ;

Forbes, S ;

Clements, J ;

Pettett, R ;

Dogan, A ;

Flanagan, A ;

Teague, J ;

Futreal, PA ;

Stratton, MR ;

Wooster, R .

BRITISH JOURNAL OF CANCER, 2004, 91 (02) :355-358

[5] RETRACTED: Over-Expression of FoxM1 Leads to Epithelial-Mesenchymal Transition and Cancer Stem Cell Phenotype in Pancreatic Cancer Cells (Retracted article. See vol. 117, pg. 1963, 2016) [J].

Bao, Bin ;

Wang, Zhiwei ;

Ali, Shadan ;

Kong, Dejuan ;

Banerjee, Sanjeev ;

Ahmad, Aamir ;

Li, Yiwei ;

Azmi, Asfar S. ;

Miele, Lucio ;

Sarkar, Fazlul H. .

JOURNAL OF CELLULAR BIOCHEMISTRY, 2011, 112 (09) :2296-2306

[6] Functional Polymorphisms in the TERT Promoter Are Associated with Risk of Serous Epithelial Ovarian and Breast Cancers [J].

Beesley, Jonathan ;

Pickett, Hilda A. ;

Johnatty, Sharon E. ;

Dunning, Alison M. ;

Chen, Xiaoqing ;

Li, Jun ;

Michailidou, Kyriaki ;

Lu, Yi ;

Rider, David N. ;

Palmieri, Rachel T. ;

Stutz, Michael D. ;

Lambrechts, Diether ;

Despierre, Evelyn ;

Lambrechts, Sandrina ;

Vergote, Ignace ;

Chang-Claude, Jenny ;

Nickels, Stefan ;

Vrieling, Alina ;

Flesch-Janys, Dieter ;

Wang-Gohrke, Shan ;

Eilber, Ursula ;

Bogdanova, Natalia ;

Antonenkova, Natalia ;

Runnebaum, Ingo B. ;

Doerk, Thilo ;

Goodman, Marc T. ;

Lurie, Galina ;

Wilkens, Lynne R. ;

Matsuno, Rayna K. ;

Kiemeney, Lambertus A. ;

Aben, Katja K. H. ;

Marees, Tamara ;

Massuger, Leon F. A. G. ;

Fridley, Brooke L. ;

Vierkant, Robert A. ;

Bandera, Elisa V. ;

Olson, Sara H. ;

Orlow, Irene ;

Rodriguez-Rodriguez, Lorna ;

Cook, Linda S. ;

Le, Nhu D. ;

Brooks-Wilson, Angela ;

Kelemen, Linda E. ;

Campbell, Ian ;

Gayther, Simon A. ;

Ramus, Susan J. ;

Gentry-Maharaj, Aleksandra ;

Menon, Usha ;

Ahmed, Shahana ;

Baynes, Caroline .

PLOS ONE, 2011, 6 (09)

[7] p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis [J].

Bergamaschi, D ;

Gasco, M ;

Hiller, L ;

Sullivan, A ;

Syed, N ;

Trigiante, G ;

Yulug, I ;

Merlano, M ;

Numico, G ;

Comino, A ;

Attard, M ;

Reelfs, O ;

Gusterson, B ;

Bell, AK ;

Heath, V ;

Tavassoli, M ;

Farrell, PJ ;

Smith, P ;

Lu, X ;

Crook, T .

CANCER CELL, 2003, 3 (04) :387-402

[8] Pancreatic cancer stem cells: Fact or fiction? [J].

Bhagwandin, Vikash J. ;

Shay, Jerry W. .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2009, 1792 (04) :248-259

[9] Detecting early pancreatic cancer: Problems and prospects [J].

Chari, Suresh T. .

SEMINARS IN ONCOLOGY, 2007, 34 (04) :284-294

[10] Multiple variants of TERT and CLPTM1L constitute risk factors for lung adenocarcinoma [J].

Chen, X. F. ;

Cai, S. ;

Chen, Q. G. ;

Ni, Z. H. ;

Tang, J. H. ;

Xu, D. W. ;

Wang, X. B. .

GENETICS AND MOLECULAR RESEARCH, 2012, 11 (01) :370-378

← 1 2 3 4 5 6 7 8 →