A stochastic model for cancer stem cell origin in metastatic colon cancer

被引:126
作者
Odoux, Christine [1 ]
Fohrer, Helene [1 ]
Hoppo, Toshitaka [1 ]
Guzik, Lynda [1 ]
Stolz, Donna Beer [2 ]
Lewis, Dale W. [4 ,5 ]
Gollin, Susanne M. [4 ,5 ]
Gamblin, T. Clark [3 ]
Geller, David A. [3 ]
Lagasse, Eric [1 ]
机构
[1] Univ Pittsburgh, Sch Med, McGowan Inst Regenerat Med, Dept Pathol, Pittsburgh, PA 15219 USA
[2] Univ Pittsburgh, Sch Med, Ctr Biol Imaging, Dept Cell Biol & Physiol, Pittsburgh, PA 15219 USA
[3] Univ Pittsburgh, Sch Med, Liver Canc Ctr, Starzl Transplant Inst,Dept Surg, Pittsburgh, PA 15219 USA
[4] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA
[5] Univ Pittsburgh, Inst Canc, Cytogenet Facil, Pittsburgh, PA USA
关键词
D O I
10.1158/0008-5472.CAN-07-5779
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Human cancers have been found to include transformed stem cells that may drive cancer progression to metastasis. Here, we report that metastatic colon cancer contains clonally derived tumor cells with all of the critical properties expected of stein cells, including self-renewal and the ability to differentiate into mature colon cells. Additionally, when injected into mice, these cells initiated tumors that closely resemble human cancer. Karyotype analyses of parental and clonally derived tumor cells expressed many consistent (clonal) along with unique chromosomal aberrations, suggesting the presence of chromosomal instability in the cancer stein cells. Thus, this new model for cancer origin and metastatic progression includes features of both the hierarchical model for cancerous stein cells and the stochastic model, driven by the observation of chromosomal instability.
引用
收藏
页码:6932 / 6941
页数:10
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