The critical role of CD133+CD44+/high tumor cells in hematogenous metastasis of liver cancers
The critical role of CD133+CD44+/high tumor cells in hematogenous metastasis of liver cancers
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DOI：
10.1038/cr.2011.139
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发表时间：
2012-01-01
期刊：
影响因子：
44.1
通讯作者：
Wang, Yizheng
中科院分区：
文献类型：
--
作者：
Hou, Ying;Zou, Qifei;Wang, Yizheng
转移性肝细胞癌（HCC）是世界范围内最致命的癌症之一。然而，负责其转移的细胞群在很大程度上仍然未知。在这里，我们报道了CD 133（+）CD 44（+/高）定义了一个负责肝癌血行转移的肿瘤细胞亚群。免疫组化结果显示，CD 133（+）和CD 44（+）肝癌细胞数量增加，且与门静脉浸润有关。纯化的CD 133（+）或CD 44（高）HCC细胞分别在克隆形成生长和血管侵袭方面具有上级优势。因此，CD 133和CD 44的组合用于定义新的HCC亚群。CD 133（+）CD 44（高），而不是CD 133（+）CD 44（低/-），CD 133-CD 44（高）或CD 133-CD 44（低/-）异种移植物在裸鼠中产生肝内或肺转移。流式细胞术进一步分析人肝癌标本显示，CD 133（+）CD 44（+）肿瘤细胞数与门静脉转移相关。从转移性HCC患者中分离的CD 133（+）CD 44（+）和CD 133（+）CD 44-肿瘤细胞的cDNA微阵列分析显示，这些细胞由具有不同基因表达谱的两个不同群体组成。我们的研究结果表明，CD 133（+）CD 44（+）肿瘤细胞是一个特殊的群体负责在肝癌的血行转移，这些细胞可能是治疗肝癌转移的目标。
Metastatic hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. However, the cell population responsible for its metastasis remains largely unknown. Here, we reported that CD133(+) CD44(+/high) defined a subgroup of tumor cells that was responsible for hematogenous metastasis of liver cancers. Immunohistochemical investigation of human HCC specimens revealed that the number of CD133(+) and CD44(+) HCC cells was increased and was associated with portal vein invasion. Purified CD133(+) or CD44(high) HCC cells were superior in clonogenic growth and vascular invasion, respectively. Thus, the combination of CD133 and CD44 was used to define a novel HCC sub-population. CD133(+) CD44(high), but not CD133(+) CD44(low/-), CD133-CD44(high) or CD133-CD44(low/-) xenografts, produced intrahepatic or lung metastasis in nude mice. Further analysis of human HCC samples by flow cytometry showed that the number of CD133(+) CD44(+) tumor cells was associated with portal vein metastasis. The cDNA microarray analysis of CD133(+) CD44(+) and CD133(+) CD44-tumor cells isolated from metastatic HCC patients revealed that these cells comprised of two different populations possessing distinct gene expression profiles. Our results suggest that CD133(+) CD44(+) tumor cells are a particular population responsible for hematogenous metastasis in liver cancers and that these cells might be targets for treatment of HCC metastasis.