Highly enriched CD133+CD44+ stem-like cells with CD133+CD44high metastatic subset in HCT116 colon cancer cells
Highly enriched CD133+CD44+ stem-like cells with CD133+CD44high metastatic subset in HCT116 colon cancer cells
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DOI：
10.1007/s10585-011-9407-7
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发表时间：
2011-12-01
影响因子：
4
通讯作者：
Liang, Hou-jie
中科院分区：
文献类型：
--
作者：
Chen, Ke-li;Pan, Feng;Liang, Hou-jie
干细胞样癌细胞（slcc）是结肠癌中独特的细胞亚群，对肿瘤维持至关重要。先前的研究表明，在给定的癌症模型中，slcc仅占很小的子集。然而，我们发现slcc的频率在一组结肠癌细胞系中有所不同，HCT116细胞主要由slcc组成，结肠圈形成能力和CD133表达证明了这一点。事实上，流式细胞术分析显示，超过60%的HCT116细胞共表达了假定的slcc标记物CD133和CD44。与非CD133(+)CD44（+）细胞相比，FACS分类的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小鼠中表现出增强的致瘤性。1000个CD133(+)CD44（+）细胞能有效启动异种移植物肿瘤（3/6），而1 × 10(5)个非CD133(+)CD44（+）细胞只能形成可触及的结节，生长速度慢得多（1/6）。更有趣的是，长期培养的自我更新的CD133(+)CD44（+）细胞富集CD133(+)CD44（高）亚群，表达上皮向间充质过渡标记，在体外更具侵袭性，体内仅负责肝转移。总之，这些数据首次证明CD133(+)CD44(+) slcc在HCT116细胞中高度富集，并且转移性slcc仅存在于CD133(+)CD44（高）亚群中。
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 x 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.