腫瘤干細胞學(xué)說認為在腫瘤中只有一小部分細胞能通過自我更新和分化再生出新的腫瘤,。過去,，CD133被認為是結(jié)腸癌干細胞的表面標(biāo)記，并且認為只有表達CD133的腫瘤細胞才能生成新的腫瘤,。
近日,，美國霍華德休斯醫(yī)學(xué)院的新研究挑戰(zhàn)了這一傳統(tǒng)觀點。Shmelkov等人利用CD133啟動子驅(qū)動報告基因lacZ轉(zhuǎn)基因小鼠模型發(fā)現(xiàn),，CD133廣泛表達于結(jié)腸中正常的已分化的表皮細胞,。并且，AC133抗體染色證實,，成年小鼠和人類所有的結(jié)腸內(nèi)腔表皮細胞都表達CD133,。通過利用攜帶CD133報告基因的小鼠和IL-10基因敲除的小鼠雜交以培育出攜帶CD133報告基因的自發(fā)型結(jié)腸癌小鼠證明，和人的原發(fā)性結(jié)腸癌一樣,，鼠的原發(fā)性結(jié)腸癌樣品中所有的表皮細胞都表達CD133，而非表皮細胞不表達CD133,。然而,，令人驚奇的是，在結(jié)腸癌已轉(zhuǎn)移至肝臟的不同病人的腫瘤樣品中,，有的表達CD133,，有的不表達CD133。將表達CD133和不表達CD133的腫瘤細胞移植到NOD/SCID的小鼠體內(nèi),，則兩種細胞都能很快地生成腫瘤。而且,，不表達CD133的腫瘤細胞更具有侵略性,，形成腫瘤的速度更快，說明轉(zhuǎn)移的結(jié)腸癌細胞不論是否表達CD133,，都具有引發(fā)腫瘤生成的能力,。因此，CD133不能作為結(jié)腸癌干細胞特異性的表面標(biāo)記,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
