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ESM-1 silencing decreased cell survival, migration, and invasion and modulated cell cycle progression in hepatocellular carcinoma

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Abstract

Endothelial cell-specific molecule-1 (ESM-1) is a secretory proteoglycan comprising a mature polypeptide of 165 amino acids and a single dermatan sulfate. The aim of this study was to evaluate endothelial cell-specific molecule-1 (ESM-1) as a hepatocellular carcinoma (HCC) marker and to analyze the effect of ESM-1 gene silencing in hepatocellular carcinoma cells. RT-PCR and Western Blot analysis revealed overexpression of ESM-1 in human HCC liver tissue and in serum from patients with HCC. Sandwich ELISA assay was used for quantitative analysis of ESM-1 in serum. Levels of ESM-1 were significantly elevated in the serum of patients with HCC (n = 40) as compared to serum from patients with hepatitis (AH, n = 40; CH, n = 39) or liver cirrhosis (n = 40) or from healthy subjects (n = 40). The accuracy of ESM-1 for HCC was higher than that of α-fetoprotein (AFP) according to ROC curve analysis. Expression of ESM-1 siRNA decreased cell survival through the inhibition of NF-κB pathway and induced cell cycle arrest by PTEN induction resulting in the inhibition of cyclin D1 in SK-Hep1 cells. Furthermore, ESM-1 silencing inhibited cell migration and invasion of SK-Hep1 cells. This study demonstrates that ESM-1 as a potential tumor marker is overexpressed in most tissues and serum in the presence of HCC and is involved with cell survival, cell cycle progression, migration, and invasion of hepatocellular carcinoma cells. Based on our results, we suggest that ESM-1 or a combination of ESM-1 and AFP is useful markers for diagnosis of HCC and ESM-1 may be useful therapeutic target of hepatocellular carcinoma.

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Acknowledgments

We thank the staff of the Kangnam St. Mary’s Hospital (Seoul, Republic of Korea) for supplying serum samples and BioInfra Inc. (Seoul, Korea) for analysis of AFP. This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF, 20100011583) and a KRIBB Research Initiative fund from the Ministry of Education, Science and Technology (MEST) provided by the Korean Government. No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Medical Genomics Research Center, KRIBB, Daejeon, 305-806, Korea

    Yun Hee Kang, Na Young Ji, Chung Il Lee, Hee Gu Lee, Jae Wha Kim, Young IL Yeom & Eun Young Song

  2. Department of Internal Medicine, Chonbuk National University Medical School and Hospital, Jeonju, Korea

    Dae Ghon Kim

  3. Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea

    Seung Kew Yoon

  4. Department of Laboratory Medicine, Dankook University School of Medicine, Cheonan, Korea

    Jong Wan Kim

  5. BioInfra. Inc., Seoul, Korea

    Pil Je Park

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  1. Yun Hee Kang
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Correspondence to Eun Young Song.

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Y.H. Kang and N.Y. Ji contributed equally to this work.

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Kang, Y.H., Ji, N.Y., Lee, C.I. et al. ESM-1 silencing decreased cell survival, migration, and invasion and modulated cell cycle progression in hepatocellular carcinoma. Amino Acids 40, 1003–1013 (2011). https://doi.org/10.1007/s00726-010-0729-6

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  • DOI: https://doi.org/10.1007/s00726-010-0729-6

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