Dysadherin can enhance tumorigenesis by conferring properties of stem-like cells to hepatocellular carcinoma cells

Park, Jeong-Ran; Kim, Ran-Ju; Lee, Yoo-Kyung; Kim, Soo-Rim; Roh, Kyung-Jin; Oh, Seung Hyun; Kong, Gu; Kang, Kyung-Sun; Nam, Jeong-Seok

doi:10.1016/j.jhep.2010.06.026

« Previous Next »Journal of Hepatology
Volume 54, Issue 1 , Pages 122-131, January 2011

Dysadherin can enhance tumorigenesis by conferring properties of stem-like cells to hepatocellular carcinoma cells

Jeong-Ran Park
- Laboratory of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, South Korea
- These authors contributed equally to this work.
Ran-Ju Kim
- Laboratory of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, South Korea
- These authors contributed equally to this work.
Yoo-Kyung Lee
- Laboratory of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, South Korea
Soo-Rim Kim
- Laboratory of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, South Korea
Kyung-Jin Roh
- Laboratory of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, South Korea
Seung Hyun Oh
- Division of Cancer Biology, National Cancer Center, Goyang, South Korea
Gu Kong
- Department of Pathology, College of Medicine, Hanyang University, Seoul, South Korea
Kyung-Sun Kang
- Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, Seoul, South Korea
Jeong-Seok Nam
- Laboratory of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, South Korea
- Corresponding author. Tel./fax: +82 32 899 6072/6350.

Received 10 March 2010; received in revised form 27 May 2010; accepted 2 June 2010. published online 31 August 2010.

Background & Aims

Hepatocellular carcinoma (HCC) is associated with a high potential for metastasis and disease recurrence, even after surgical resection. The cancer stem cell (CSC) hypothesis proposes that CSCs are responsible for chemo-resistance, recurrence, and metastasis. Dysadherin is a prognostic indicator of metastasis and poor survival in many different cancer types. In this study, we investigated the possible link between dysadherin and CSC in HCC.

Methods

We analyzed the functional implications of dysadherin on cancer stemness by modification of the dysadherin gene in HCC cell lines.

Results

The transfection of dysadherin cDNA into the liver cancer cell line PLC/PRF/5 enhanced the properties of CSCs, including anti-apoptosis, their sphere-forming ability, side population phenotype, and tumor initiation ability in vivo. Furthermore, knockdown of dysadherin in the liver cancer cell line SK-Hep1 suppressed its stem cell-like properties.

Conclusions

These results show that dysadherin give rise to properties of CSC in HCC. Therefore, these findings suggest that dysadherin may be a potential molecular prognostic marker of HCC and may aid in the development of more effective therapies.

Keywords: Dysadherin, Hepatocellular carcinoma, Cancer stem cell, Side population

Abbreviations: HCC, hepatocellular carcinoma, DMEM, Dulbecco’s modified Eagle’s medium, FBS, fetal bovine serum, PPIA, cyclophilin A, MTT, 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, PBS, phosphate-buffered saline, SD, standard deviation