肿瘤干细胞学说认为在肿瘤中只有一小部分细胞能通过自我更新和分化再生出新的肿瘤。过去，CD133被认为是结肠癌干细胞的表面标记，并且认为只有表达CD133的肿瘤细胞才能生成新的肿瘤。
近日，美国霍华德休斯医学院的新研究挑战了这一传统观点。Shmelkov等人利用CD133启动子驱动报告基因lacZ转基因小鼠模型发现，CD133广泛表达于结肠中正常的已分化的表皮细胞。并且，AC133抗体染色证实，成年小鼠和人类所有的结肠内腔表皮细胞都表达CD133。通过利用携带CD133报告基因的小鼠和IL-10基因敲除的小鼠杂交以培育出携带CD133报告基因的自发型结肠癌小鼠证明，和人的原发性结肠癌一样，鼠的原发性结肠癌样品中所有的表皮细胞都表达CD133，而非表皮细胞不表达CD133。然而，令人惊奇的是，在结肠癌已转移至肝脏的不同病人的肿瘤样品中，有的表达CD133，有的不表达CD133。将表达CD133和不表达CD133的肿瘤细胞移植到NOD/SCID的小鼠体内，则两种细胞都能很快地生成肿瘤。而且，不表达CD133的肿瘤细胞更具有侵略性，形成肿瘤的速度更快，说明转移的结肠癌细胞不论是否表达CD133，都具有引发肿瘤生成的能力。因此，CD133不能作为结肠癌干细胞特异性的表面标记。（生物谷Bioon.com）
生物谷推荐原始出处：
J. Clin. Invest. 118(6): 2111-2120 (2008). doi:10.1172/JCI34401.
CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumor
Sergey V. Shmelkov1, Jason M. Butler1, Andrea T. Hooper1, Adilia Hormigo1, Jared Kushner1, Till Milde1, Ryan St. Clair1, Muhamed Baljevic1, Ian White1, David K. Jin1, Amy Chadburn1, Andrew J. Murphy2, David M. Valenzuela2, Nicholas W. Gale2, Gavin Thurston2, George D. Yancopoulos2, Michael D’Angelica3, Nancy Kemeny3, David Lyden1 and Shahin Rafii1
Colon cancer stem cells are believed to originate from a rare population of putative CD133+ intestinal stem cells. Recent publications suggest that a small subset of colon cancer cells expresses CD133, and that only these CD133+ cancer cells are capable of tumor initiation. However, the precise contribution of CD133+ tumor-initiating cells in mediating colon cancer metastasis remains unknown. Therefore, to temporally and spatially track the expression of CD133 in adult mice and during tumorigenesis, we generated a knockin lacZ reporter mouse (CD133lacZ/+), in which the expression of lacZ is driven by the endogenous CD133 promoters. Using this model and immunostaining, we discovered that CD133 expression in colon is not restricted to stem cells; on the contrary, CD133 is ubiquitously expressed on differentiated colonic epithelium in both adult mice and humans. Using Il10–/–CD133lacZ mice, in which chronic inflammation in colon leads to adenocarcinomas, we demonstrated that CD133 is expressed on a full gamut of colonic tumor cells, which express epithelial cell adhesion molecule (EpCAM). Similarly, CD133 is widely expressed by human primary colon cancer epithelial cells, whereas the CD133– population is composed mostly of stromal and inflammatory cells. Conversely, CD133 expression does not identify the entire population of epithelial and tumor-initiating cells in human metastatic colon cancer. Indeed, both CD133+ and CD133– metastatic tumor subpopulations formed colonospheres in in vitro cultures and were capable of long-term tumorigenesis in a NOD/SCID serial xenotransplantation model. Moreover, metastatic CD133– cells form more aggressive tumors and express typical phenotypic markers of cancer-initiating cells, including CD44 (CD44+CD24–), whereas the CD133+ fraction is composed of CD44lowCD24+ cells. Collectively, our data suggest that CD133 expression is not restricted to intestinal stem or cancer-initiating cells, and during the metastatic transition, CD133+ tumor cells might give rise to the more aggressive CD133– subset, which is also capable of tumor initiation in NOD/SCID mice.
