Identification and characterization of tumorigenic liver cancer stem/progenitor cells.
OBJECTIVE
Recent efforts in stem cell biology suggest that tumors are organized in a hierarchy of heterogeneous cell populations and that the capability to maintain tumor formation/growth specifically resides in a small population of cells called cancer stem cells (CSCs). The aim of this study is to identify, isolate, and characterize the CSC population that drives and maintains hepatocellular carcinoma (HCC) growth and metastasis.


METHODS
Normal stem cells involved in liver regeneration were identified using a severe partial hepatectomy model. Purified HCC cells, with or without expression of the identified normal stem cell phenotype, were evaluated, based on their tumorigenic potential and exhibition of defined stem/progenitor cell-like properties, to determine whether liver CSCs can be or partly be identified by this surface marker.


RESULTS
We report the identification and isolation of a population of CSCs expressing a CD133 surface phenotype from human liver cell lines. CD133(+) cells possess a greater colony-forming efficiency, higher proliferative output, and greater ability to form tumor in vivo. These cells are endowed with characteristics similar to those of progenitor cells including the expression of "stemness" genes, the ability to self-renew, and the ability to differentiate into nonhepatocyte-like lineages. Furthermore, CD133 is found to represent only a minority of the tumor cell population in human HCC specimens.


CONCLUSIONS
We report the identification of a CSC population in HCC characterized by their CD133 phenotype. The identification of tumorigenic liver CSCs could provide new insight into the HCC tumorigenic process and possibly bear great therapeutic implications.
Ma
Stephanie
S
Department of Pathology, The University of Hong Kong, Pokfulam, Hong Kong, China.
Chan
Kwok-Wah
KW
Hu
Liang
L
Lee
Terence Kin-Wah
TK
Wo
Jana Yim-Hung
JY
Ng
Irene Oi-Lin
IO
Zheng
Bo-Jian
BJ
Guan
Xin-Yuan
XY
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism; D015197:Carcinogenicity Tests; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D002469:Cell Separation; D015870:Gene Expression; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008115:Liver Regeneration; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D024510:Muscle Development; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D010455:Peptides / Q000378:metabolism*; D010641:Phenotype; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology*; D014183:Transplantation, Heterologous
D000071916:AC133 Antigen; D015703:Antigens, CD; D000943:Antigens, Differentiation; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse