The critical role of CD133 CD44 tumor cells in hematogenous metastasis of liver cancers

• Published in: Cell research 2012-01, Vol.22 (1), p.259-272
• Main Authors: Hou, Ying, Zou, Qifei, Ge, Ruiliang, Shen, Feng, Wang, Yizheng
• Format: Article
• Language: English
• Subjects: AC133 Antigen; Animals; Antigens, CD - metabolism; Biomarkers, Tumor - metabolism; Cell Count; Gene Expression Profiling; Glycoproteins - metabolism; Hep G2 Cells; Humans; Hyaluronan Receptors - metabolism; Immunohistochemistry; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Neoplasm Metastasis - pathology; Neoplasms, Vascular Tissue - secondary; Oligonucleotide Array Sequence Analysis; Peptides - metabolism; Portal Vein - metabolism; Portal Vein - pathology
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/cr.2011.139

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.