State Key Laboratory of Neuroscience, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Shanghai, China.
Cell Res. 2012 Jan;22(1):259-72. doi: 10.1038/cr.2011.139. Epub 2011 Aug 23.
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.
转移性肝细胞癌 (HCC) 是全球最致命的癌症之一。然而，负责其转移的细胞群体在很大程度上仍不清楚。在这里，我们报告 CD133(+)CD44(+/高) 定义了一个负责肝癌血行转移的肿瘤细胞亚群。对人 HCC 标本的免疫组织化学研究表明，CD133(+)和 CD44(+) HCC 细胞的数量增加，并与门静脉侵犯有关。纯化的 CD133(+)或 CD44(high) HCC 细胞在集落形成生长和血管侵袭方面分别具有优势。因此，CD133 和 CD44 的组合用于定义 HCC 的一个新亚群。CD133(+)CD44(high)，而不是 CD133(+)CD44(low/-)、CD133(-)CD44(high)或 CD133(-)CD44(low/-)异种移植物，在裸鼠中产生肝内或肺转移。通过流式细胞术对人 HCC 样本的进一步分析表明，CD133(+)CD44(+)肿瘤细胞的数量与门静脉转移有关。对来自转移性 HCC 患者分离的 CD133(+)CD44(+)和 CD133(+)CD44(-)肿瘤细胞的 cDNA 微阵列分析表明，这些细胞包含两个具有不同基因表达谱的不同群体。我们的结果表明，CD133(+)CD44(+)肿瘤细胞是负责肝癌血行转移的一个特定群体，这些细胞可能是 HCC 转移治疗的靶点。
