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A decade’s studies on metastasis of hepatocellular carcinoma

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Abstract

Metastasis remains one of the major challenges before hepatocellular carcinoma (HCC) is finally conquered. This paper summarized a decade’s studies on HCC metastasis at the Liver Cancer Institute of Fudan University. We have established a stepwise metastatic human HCC model system, which included a metastatic HCC model in nude mice (LCI-D20), a HCC cell line with high metastatic potential (MHCC97), a relatively low metastatic potential cell clone (MHCC97L) and several stepwise high metastatic potential cell clones (MHCC97H, HCCLM3, and HCCLM6) from their parent MHCC97 cell. Endeavors have been made for searching human HCC metastasis-related chromosomes/proteins/genes. Monogene-based studies revealed that HCC invasion/metastasis was similar to that of other solid tumors, and the biological characteristics of small HCC were only slightly better than that of large HCC. Using comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), genotyping, cDNA microarray, and 2-dimensional gel electrophoresis, we obtained some interesting results. In particular, in collaboration with the National Institute of Health (NIH) in the United States, we generated a molecular signature that can classify metastatic HCC patients, identified osteopontin as a lead gene in the signature, and found that genes favoring metastasis progression were initiated in the primary tumors. We also found that chromosome 8p deletion, particularly in the region of 8p23, was associated with HCC metastasis. Cytokeratin 19 was identified as one of the proteins, which was found in MHCC97H, but not in MHCC97L cells. Experimental interventions using the high metastatic nude mice model have provided clues for the prevention of HCC metastasis. Translation from workbench to bedside demonstrated that serum VEGF, microvessel density, and p53 scoring may be of value for the prediction of postoperative metastatic recurrence. Interferon alpha proved effective for the prevention of recurrence both experimentally and clinically. In conclusion, HCC metastasis that probably initiated in the primary tumor is a multigene-involved, multistep, and changing process. The further elucidation of the mechanism underlying HCC metastasis will provide a more solid basis for the prediction and prevention of the metastatic recurrence of HCC.

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Acknowledgments

We thank Fan-Xian Sun, Jian Tian, Qiong Xue, and Jie Chen for the establishment of metastatic models; Qi Zheng, Xiao-Ming Li, Qi Niu, and Xiao-Feng Wu for studies of metastatic predictors; Ming Yao and Lian-Hai Zhang for studies on metastasis-related genes and chromosomes; Yong Liao and Jing-Jing Sun for experimental interventions. These studies were supported in part by the State Key Basic Research Program of China (G1998051211), Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, and the Fund for Leading Specialty of Shanghai Metropolitan Bureau of Health 983001.

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  1. Liver Cancer Institute, Zhongshan Hospital, 136 Yi Xue Yuan Road, 200032, Shanghai, P. R. China

    Zhao-You Tang, Sheng-Long Ye, Yin-Kun Liu, Lun-Xiu Qin, Hui-Chuan Sun, Qin-Hai Ye, Lu Wang, Jian Zhou, Shuang-Jian Qiu, Yan Li, Xue-Ning Ji, Hu Liu, Jing-Ling Xia, Zhi-Quan Wu, Jia Fan, Zeng-Chen Ma, Xin-Da Zhou, Zhi-Ying Lin & Kang-Da Liu

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  1. Zhao-You Tang
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Correspondence to Zhao-You Tang.

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Tang, ZY., Ye, SL., Liu, YK. et al. A decade’s studies on metastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol 130, 187–196 (2004). https://doi.org/10.1007/s00432-003-0511-1

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