한빛사 논문
Abstract
Jin Sil Chung,* Sunhoo Park,‡ Seon Ho Park,* Eun-Ran Park,§ Pu-Hyeon Cha,§ Bu-Yeo Kim,§,∥ Young Min Chung,* Seon Rang Woo,§ Chul Ju Han,¶ Sang-Bum Kim,# Kyung-Suk Suh,** Ja-June Jang,‡‡ Kyoungbun Lee,‡‡ Dong Wook Choi,§§ Sora Lee,* Gi Young Lee,* Ki Baik Hahm,∥ ∥ Jung Ar Shin,*,¶¶ Byung Soo Kim,## Kyung Hee Nho,*** Tae Woo Kim,*** Kee-Ho Lee,§ and Young Do Yoo*
*Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University College of Medicine, Seoul; ‡Department of Pathology, §Division of Radiation Cancer Research, ¶Department of Internal Medicine, and #Department of Surgery, Korea Institute of Radiological and Medical Sciences, Seoul; ∥ Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon; **Department of Surgery and ‡‡Department of Pathology, Seoul National University School of Medicine, Seoul; §§Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; ∥ ∥Lab of Translational Medicine Gachon University Lee Gil Ya Cancer and Diabetes Institute, Incheon; ¶¶Department of Internal Medicine, Yonsei University College of Medicine, Seoul; and ##Department of Internal Medicine and ***Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Seoul, Republic of Korea
Corresponding authors : Kee-Ho Lee and Young Do Yoo
Abstract
Background & Aims:
Chronic oxidative stress from reactive oxygen species (ROS) produced by the mitochondria promotes hepatocarcinogenesis and tumor progression. However, the exact mechanism by which mitochondrial ROS contributes to tumor cell invasion is not known. We investigated expression the role of ROS modulator 1 (Romo1) in hepatocellular carcinoma (HCC) development and tumor cell invasiveness.
Methods:
We performed real-time, semi-quantitative, reverse transcriptase-PCR; invasion and luciferase assays; and immunofluorescence and immunohistochemical analyses. The formation of pulmonary metastatic nodules after tumor cell injection was tested in severe combined immunodeficient mice. We analyzed Romo1 expression in HCC cell lines and tissues (n = 95).
Results:
Expression of Romo1 was increased in HCC cells, compared to normal human lung fibroblast cells. Exogenous expression of Romo1 in HCC cells increased their invasive activity, compared with control cells. Knockdown of Romo1 in Hep3B and Huh-7 HCC cells reduced their invasive activity in response to stimulation with 12-O-tetradecanoylphorbol-13-acetate. Levels of Romo1 were increased, compared with normal liver tissues, in 63 of 95 HCC samples from patients. In HCC samples from patients, there was an inverse correlation between Romo1 overexpression and patient survival times. Increased levels Romo1 also correlated with vascular invasion by the tumors, reduced differentiation, and larger tumor size.
Conclusions:
Romo1 is a biomarker of HCC progression that might be used in diagnosis. Reagents that inhibit activity of Romo1 and suppress mitochondrial ROS production, rather than eliminate upregulated intracellular ROS, might be developed as cancer therapies.
Keywords: Liver Cancer , metastasis , chemotherapy resistance , prognostic factor
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