Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Clin Exp Metastasis. 2011 Dec;28(8):751-63. doi: 10.1007/s10585-011-9407-7. Epub 2011 Jul 13.
Stem-like cancer cells (SLCCs) are distinct cellular subpopulation in colon cancer that is essential for tumor maintenance. Previous studies indicated that SLCCs accounted for only a minor subset in a given cancer model. However, we found that SLCCs frequency varied among a panel of colon cancer cell lines, with HCT116 cells composed mainly of SLCCs, as demonstrated by colonosphere forming capability and CD133 expression. Indeed, flow cytometric analysis revealed more than 60% HCT116 cells co-expressed the putative SLCCs markers CD133 and CD44. Compared with non-CD133(+)CD44(+) cells, FACS sorted CD133(+)CD44(+) cells were undifferentiated, endowed with extensive self-renewal and epithelial lineage differentiation capacity in vitro. CD133(+)CD44(+) exhibited enhanced tumorigeneicity in NOD/SCID mice. One thousand CD133(+)CD44(+) cells initiated xenograft tumors efficiently (3/6) while 1 × 10(5) non-CD133(+)CD44(+) cells could only form palpable nodule with much slower growth rate (1/6). More interestingly, long-term cultured self-renewing CD133(+)CD44(+) cells enriched CD133(+)CD44(high) subset, which expressed epithelial to mesenchymal transition marker, were more invasive in vitro and responsible solely for liver metastasis in vivo. In conclusion, these data demonstrated for the first time that CD133(+)CD44(+) SLCCs were highly enriched in HCT116 cells and that metastatic SLCCs resided exclusively in a CD133(+)CD44(high) subpopulation.
肿瘤干细胞（SLCCs）是结肠癌中一种独特的细胞亚群，对于肿瘤的维持至关重要。先前的研究表明，SLCCs 在给定的癌症模型中仅占一小部分。然而，我们发现 SLCCs 的频率在一系列结肠癌细胞系中有所不同，HCT116 细胞主要由 SLCCs 组成，这可以通过其形成类器官的能力和 CD133 表达来证明。事实上，流式细胞术分析显示，超过 60%的 HCT116 细胞共同表达了假定的 SLCCs 标志物 CD133 和 CD44。与非 CD133(+)CD44(+)细胞相比，FACS 分选的 CD133(+)CD44(+)细胞未分化，具有广泛的自我更新和上皮谱系分化能力。CD133(+)CD44(+)在 NOD/SCID 小鼠中具有更强的致瘤性。1000 个 CD133(+)CD44(+)细胞能够有效地启动异种移植肿瘤（3/6），而 1×10(5)个非 CD133(+)CD44(+)细胞只能形成可触及的结节，生长速度较慢（1/6）。更有趣的是，长期培养的自我更新的 CD133(+)CD44(+)细胞富集了 CD133(+)CD44(high)亚群，该亚群表达上皮间质转化标志物，在体外具有更强的侵袭性，并且是体内肝转移的唯一原因。总之，这些数据首次表明，CD133(+)CD44(+) SLCCs 在 HCT116 细胞中高度富集，而转移性 SLCCs 仅存在于 CD133(+)CD44(high)亚群中。
