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Clusterin plays an important role in hepatocellular carcinoma metastasis

Oncogene volume 25, pages 1242–1250 (2006)Cite this article

Abstract

To identify genes associated with tumor metastasis in hepatocellular carcinoma (HCC), gene expression profiles between a pair of primary HCC (H2-P) and their matched metastatic HCC (H2-M) were compared. Overexpression of clusterin (CLU) was found in H2-M cells. To determine the roles CLU played in HCC metastasis, CLU was transfected into H2-P cells. Overexpression of CLU in H2-P cells increased cell migration by twofold in vitro and formation of metastatic tumor nodules in liver by eightfold in vivo. To evaluate the correlation of CLU expression with HCC metastasis, the expression levels of CLU in HCCs were investigated using a tissue microarray (TMA) containing 104 pairs of primary HCCs and their matched metastases. The frequency of CLU overexpression increased significantly in metastatic HCCs (59.1%) compared with that in primary tumors (32.6%, P<0.001). To gain additional insight into the function of CLU, the expression profile of H2P-CLU was compared with vector-transfected H2-P cells by cDNA microarray. A total of 35 upregulated and 14 downregulated genes were detected in H2P-CLU. One of the upregulated genes known as YKL-40, which is implicated in matrix-remodeling and metastasis, was further studied using TMA. A significant correlation (P<0.001) between the expression levels of YKL-40 and CLU was observed, implying that the CLU-YKL-40 pathway may play an important role in HCC metastasis.

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Acknowledgements

This study is supported in part by a Research Grant Council Grant HKU 7393/04M (Hong Kong), donations from Mr Heung Chit Kau, the Areas of Excellence Scheme (AoE/P-10/01) of the University Grants Committee (Hong Kong), and the China National ‘863’ Hi-tech Program (2003AA2Z2052).

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Authors and Affiliations

  1. Department of Clinical Oncology, The University of Hong Kong, Pokfulam, Hong Kong, China

    S H Lau, J S T Sham, D Tang, N Ma, L Hu & X-Y Guan

  2. State Key Laboratory of Oncology in Southern China, Cancer Center, Guangzhou, China

    D Xie

  3. Department of Biology and Chemistry, The City University of Hong Kong, Hong Kong, China

    C-H Tzang & M Yang

  4. Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China

    Y Wang

  5. Department of Pathology, Sun Yat-sen University, Guangzhou, China

    J-M Wen, G Xiao & W-M Zhang

  6. Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China

    G K K Lau

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  1. S H Lau
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  2. J S T Sham
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Correspondence to X-Y Guan.

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Lau, S., Sham, J., Xie, D. et al. Clusterin plays an important role in hepatocellular carcinoma metastasis. Oncogene 25, 1242–1250 (2006). https://doi.org/10.1038/sj.onc.1209141

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