The Intestinal Stem Cell Signature Identifies Colorectal Cancer Stem Cells and Predicts Disease Relapse
The Intestinal Stem Cell Signature Identifies Colorectal Cancer Stem Cells and Predicts Disease Relapse
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DOI：
10.1016/j.stem.2011.02.020
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发表时间：
2011-05-06
期刊：
影响因子：
23.9
通讯作者：
Batlle, Eduard
中科院分区：
文献类型：
--
作者：
Merlos-Suarez, Anna;Barriga, Francisco M.;Batlle, Eduard
结直肠癌（CRC）的常见并发症是治疗后肿瘤的再生。在这里，我们报告了一种对成人肠干细胞（ISCs）特异性的基因特征，可以预测CRC患者的疾病复发。ISCs以EphB2受体的高表达为标志，EphB2受体随着细胞分化而逐渐沉默。使用EphB2和ISC标记物Lgr5，我们获得了FACS纯化和分析的小鼠ISCs、隐窝增殖祖细胞和晚期瞬时扩增细胞，以定义对正常ISCs特异的基因程序。此外，我们发现ISC特异性基因识别位于肿瘤结构底部的干细胞样细胞群，使人联想到隐窝。EphB2分选的ISC样肿瘤细胞在免疫缺陷小鼠中显示出强大的肿瘤起始能力以及长期自我更新潜力。综上所述，我们的数据表明ISC计划在结直肠肿瘤中定义了一个癌症干细胞小生境，并在CRC复发中起着核心作用。
A frequent complication in colorectal cancer (CRC) is regeneration of the tumor after therapy. Here, we report that a gene signature specific for adult intestinal stem cells (ISCs) predicts disease relapse in CRC patients. ISCs are marked by high expression of the EphB2 receptor, which becomes gradually silenced as cells differentiate. Using EphB2 and the ISC marker Lgr5, we have FACS-purified and profiled mouse ISCs, crypt proliferative progenitors, and late transient amplifying cells to define a gene program specific for normal ISCs. Furthermore, we discovered that ISC-specific genes identify a stem-like cell population positioned at the bottom of tumor structures reminiscent of crypts. EphB2 sorted ISC-like tumor cells display robust tumor-initiating capacity in immunodeficient mice as well as long-term self-renewal potential. Taken together, our data suggest that the ISC program defines a cancer stem cell niche within colorectal tumors and plays a central role in CRC relapse.