转移性结肠癌中癌症干细胞起源的随机模型。
A stochastic model for cancer stem cell origin in metastatic colon cancer.
作者信息
Odoux Christine, Fohrer Helene, Hoppo Toshitaka, Guzik Lynda, Stolz Donna Beer, Lewis Dale W, Gollin Susanne M, Gamblin T Clark, Geller David A, Lagasse Eric
机构信息
McGowan Institute for Regenerative Medicine, Department of Pathology, University of Pittsburgh Medical School, 100 Technology Drive, Suite 200, Pittsburgh PA, 15219-3130, USA.
出版信息
Cancer Res. 2008 Sep 1;68(17):6932-41. doi: 10.1158/0008-5472.CAN-07-5779.
Abstract
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 stem 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 stem cells. Thus, this new model for cancer origin and metastatic progression includes features of both the hierarchical model for cancerous stem cells and the stochastic model, driven by the observation of chromosomal instability.
摘要
已发现人类癌症包含可能驱动癌症进展至转移的转化干细胞。在此，我们报告转移性结肠癌含有克隆衍生的肿瘤细胞，这些细胞具有干细胞所预期的所有关键特性，包括自我更新以及分化为成熟结肠细胞的能力。此外，当将这些细胞注入小鼠体内时，它们引发的肿瘤与人类癌症极为相似。对亲代和克隆衍生的肿瘤细胞进行的核型分析显示，除了独特的染色体畸变外，还存在许多一致的（克隆性的）染色体畸变，这表明癌症干细胞中存在染色体不稳定性。因此，这种新的癌症起源和转移进展模型兼具癌干细胞层级模型和随机模型的特征，这是由对染色体不稳定性的观察所驱动的。
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