Expression of CD133 confers malignant potential by regulating metalloproteinases in human hepatocellular carcinoma.

Abstract

BACKGROUND & AIMS:

Although CD133 expression is identified as a cancer stem cell marker of hepatocellular carcinoma (HCC), the detailed characteristics of HCC cells expressing CD133 remain unclear.

METHODS:

We examined the malignant characteristics of CD133-expressing HCC cells.

RESULTS:

CD133-expressing cells could be detected with low frequency in 5 HCC tissues. We derived two different HCC cell lines by (1) transfection of CD133 siRNA in PLC/PRF/5 cells in (CD133si-PLC/PRF/5), and (2) by a magnetic cell sorting method that allowed to divide Huh7 cells into two CD133 positive (+) and negative (-) groups. CD133 knockdown in PLC/PRF/5 cells resulted in a decrease of the mRNA and protein expressions of matrix metalloproteinase (MMP)-2 and a disintegrin and metalloproteinase (ADAM)9. We next examined the malignant characteristics related to decreasing MMP-2 and ADAM9 in HCC cells. In CD133si-PLC/PRF/5 cells and CD133- Huh7 cells, invasiveness and vascular endothelial growth factor (VEGF) production, which are both related to the activity of MMP-2, were inhibited compared CD133-expressing HCC cells. We previously demonstrated that ADAM9 protease plays critical roles in the shedding of MHC class I-related chain A (MICA) which regulates the sensitivity of tumor cells to natural killer cells (NK). Decreasing ADAM9 expression in CD133si-PLC/PRF/5 cells and CD133- Huh7 cells resulted in an increase in membrane-bound MICA and a decrease in soluble MICA production. Both CD133si-PLC/PRF/5 cells and CD133- Huh7 cells were susceptible to NK activity, depending on the expression levels of membrane-bound MICA, but CD133-expressing HCC cells were not.

CONCLUSION:

These results demonstrate that CD133 expression in HCC cells confers malignant potential which may contribute to the survival of HCC cells.

• Authors: Keisuke Kohga, Tomohide Tatsumi, Tetsuo Takehara, Hinako Tsunematsu, Satoshi Shimizu, Masashi Yamamoto, Akira Sasakawa, Takuya Miyagi, Norio Hayashi
• Journal: Journal of hepatology (J Hepatol) Vol. 52 Issue 6 Pg. 872-9 (Jun 2010) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 20395004 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• AC133 Antigen
• Antigens, CD
• Glycoproteins
• Histocompatibility Antigens Class I
• MHC class I-related chain A
• Membrane Proteins
• PROM1 protein, human
• Peptides
• Prom1 protein, mouse
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• ADAM Proteins
• ADAM9 protein, human
• MMP2 protein, human
• Matrix Metalloproteinase 2

Topics

• AC133 Antigen
• ADAM Proteins (genetics, metabolism)
• Animals
• Antigens, CD (genetics, metabolism)
• Carcinoma, Hepatocellular (metabolism, pathology, physiopathology)
• Cell Survival (physiology)
• Flow Cytometry
• Gene Expression Regulation, Neoplastic
• Glycoproteins (genetics, metabolism)
• Hep G2 Cells
• Histocompatibility Antigens Class I (metabolism)
• Humans
• Immunomagnetic Separation
• Killer Cells, Natural (pathology)
• Liver Neoplasms (metabolism, pathology, physiopathology)
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Membrane Proteins (genetics, metabolism)
• Mice
• Mice, Nude
• Neoplasm Invasiveness
• Peptides (genetics, metabolism)
• RNA Interference
• Vascular Endothelial Growth Factor A (metabolism)