Volume 22, No 1, Jan 2012

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 22 Issue 1, January 2012: 259-272

ORIGINAL ARTICLES

The critical role of CD133⁺CD44^+/high tumor cells in hematogenous metastasis of liver cancers

Ying Hou^1,2,*, Qifei Zou^3,*, Ruiliang Ge³, Feng Shen³ and Yizheng Wang¹

¹State Key Laboratory of Neuroscience, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, 320 Yueyang Road, Shanghai 200031, China
²Graduate School, The Chinese Academy of Sciences
³Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, China Correspondence: Yizheng Wang, Feng Shen,(yzwang@ion.ac.cn; shenfengdfgd@yahoo.com.cn)

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.

Cell Research (2012) 22:259-272. doi:10.1038/cr.2011.139; published online 23 August 2011

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