Establishment of human colon cancer cell lines from fresh tumors versus xenografts: Comparison of success rate and cell line features

被引:145
作者
Dangles-Marie, Virginie
Pocard, Marc
Richon, Sophie
Weiswald, Louis-Bastien
Assayag, Franck
Saulnier, Patrick
Judde, Jean-Gabriel
Janneau, Jean-Louis
Auger, Nathalie
Validire, Pierre
Dutrillaux, Bernard
Praz, Francoise
Bellet, Dominique
Poupon, Marie-France
机构
[1] Univ Paris 05, Lab Physiopathol Hepat, UMR 8149, CNRS,Fac Sci Pharmaceut & Biol Paris, F-75006 Paris, France
[2] Univ Paris 06, INSERM U762, Paris, France
[3] Inst Curie, INSERM U612, Paris, France
[4] Inst Mutualiste Montsouris, Dept Pathol Anat, Paris, France
[5] Museum Natl Hist Nat, CNRS, UMR 5202, F-75231 Paris, France
[6] Inst Gustave Roussy, Dept Chirurg, Villejuif, France
[7] Inst Gustave Roussy, Dept Biol Clin, F-94805 Villejuif, France
[8] Ctr Rene Huguenin, Nucl Med Serv, St Cloud, France
关键词
D O I
10.1158/0008-5472.CAN-06-0594
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Obtaining representative human colon cancer cell lines from fresh tumors is technically difficult. Using 32 tumor fragments from patients with colon cancer, the present study shows that prior xenograft leads to more efficient cell line establishment compared with direct establishment from fresh tumors (P < 0.05). From 26 tumor specimens, we successfully established 20 tumor xenografts in nude mice (77%); among 19 of these xenografts, 9 (47%) led to cell lines, including four from liver metastases. Only 3 of 31 tumor specimens (9.7%) grew immediately in vitro, and all were derived from primary tumors. To compare major phenotypic and genotypic characteristics of human colon cancer cell lines derived from the same tumor fragment using two protocols, the two pairs of cell lines obtained from 2 of 32 tumor fragments were extensively studied. They displayed similar morphology and were able to form compact spheroids. Chemosensitivity to 5-fluorouracil, CPT11, and L-OHP differed between cell lines obtained from patient tumors and those derived from xenografts. Matched cell lines shared a common core of karyotype alterations and distinctive additional chromosomal aberrations. Expression levels of genes selected for their role in oncogenesis evaluated by real-time quantitative PCR were found to be statistically correlated whatever the in vitro culture model used. In conclusion, xenotransplantation in mice of tumor fragments before establishment of cell lines enables generation of more novel human cancer cell lines for investigation of colon cancer cell biology, opening up the opportunity of reproducing the diversity of this disease.
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页码:398 / 407
页数:10
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