Du Lei, Wang Hongyi, He Leya, Zhang Jingyu, Ni Biyun, Wang Xiaohui, Jin Haijing, Cahuzac Nathalie, Mehrpour Maryam, Lu Youyong, Chen Quan
Joint Laboratory of Apoptosis and Cancer Biology, the State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Clin Cancer Res. 2008 Nov 1;14(21):6751-60. doi: 10.1158/1078-0432.CCR-08-1034.
Both CD44 and CD133 were reported as putative markers for isolating colorectal cancer stem cells (CSC). It remains to be resolved if both of these markers are of functional importance for colorectal CSC.
The expression of CD44 and CD133 in normal colonic tissues and primary colorectal cancer was assessed by immunohistochemistry in a series of 60 patients on tissue microarray sections. Both in vitro clonogenic and in vivo tumorigenic assay were applied to measure CSC activities from the cells isolated from patients. Lentiviral RNA interference was used to stably knock down CD44 or CD133 in colorectal cancer cells from patients.
We found that CD44(+) cells displayed clustered growth and they did not colocalize with CD133(+) cells within colorectal cancer. As few as 100 CD44(+) cells from a patients' tumor initiated a xenograft tumor in vivo. A single CD44(+) cell from a tumor could form a sphere in vitro which has characteristic stem cell properties and was able to generate a xenograft tumor resembling the properties of the primary tumor. Knockdown of CD44, but not CD133, strongly prevented clonal formation and inhibited tumorigenicity in xenograft model.
These results indicate that CD44 is a robust marker and is of functional importance for colorectal CSC for cancer initiation.
CD44和CD133均被报道为分离结直肠癌干细胞（CSC）的假定标志物。这两种标志物对于结直肠癌CSC是否均具有功能重要性仍有待解决。
通过免疫组织化学方法，在60例患者的组织微阵列切片上评估正常结肠组织和原发性结直肠癌中CD44和CD133的表达。应用体外克隆形成试验和体内致瘤试验来测量从患者分离的细胞的CSC活性。使用慢病毒RNA干扰稳定敲低患者结直肠癌细胞中的CD44或CD133。
我们发现CD44(+)细胞呈簇状生长，并且在结直肠癌中它们与CD133(+)细胞不共定位。来自患者肿瘤的仅100个CD44(+)细胞就能在体内引发异种移植肿瘤。肿瘤中的单个CD44(+)细胞在体外可形成具有特征性干细胞特性的球体，并能够产生类似于原发性肿瘤特性的异种移植肿瘤。敲低CD44而非CD133可强烈阻止异种移植模型中的克隆形成并抑制致瘤性。
这些结果表明，CD44是一种可靠的标志物，对于结直肠癌CSC的肿瘤起始具有功能重要性。
