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ORIGINAL RESEARCH ARTICLE

ßig-h3 Is Involved in the HAb18G/CD147-Mediated Metastasis Process in Human Hepatoma Cells

Juan Tang^*,1, Hong-wei Zhou^,1, Jian-li Jiang^*,1, Xiang-min Yang^*, Yu Li^*, Hong-Xin Zhang, Zhi-nan Chen^*,2 and Wei-ping Guo^,2

^* Cell Engineering Research Centre and Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an 710032, China; and Department of Interventional Radiation, Tang-Du Hospital, Fourth Military Medical University, Xi’an 710032, China

To whom requests for reprints should be addressed at ² Cell Engineering Research Centre and Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 17 Changlexi Street, Xi’an 710032, China. E-mail: znchen{at}fmmu.edu.cn or Department of Interventional Radiation, Tang-Du Hospital, Fourth Military Medical University, 17 Changlexi Street, Xi’an 710032, China. E-mail: guoweip{at}fmmu.edu.cn

HAb18G/CD147, a new hepatoma-associated antigen cloned and screened from human hepatocellular carcinoma cDNA library, is closely correlated with metastasis process in human hepatoma cells. In the present study we aimed to identify the pivotal molecules of the HAb18G/CD147 signal transduction pathway. The investigation showed that ßig-h3, a secretory extracellular matrix (ECM) protein, was upregulated in HAb18G/CD147-expressing human hepatoma T7721 cells and was downregulated by depressing HAb18G/CD147 expression. The expression of ßig-h3, upregulated in human hepatoma cells, was positively relative to the expression of HAb18G/CD147 in different human hepatoma cell lines. By overexpressing ßig-h3 in human SMMC-7721 hepatoma cells, we discovered that ßig-h3 promoted cell adhesion, invasion, and matrix metalloproteinase (MMP) secretion potential. HAb18G/CD147-induced invasion and metastasis potential of human hepatoma cells can be attenuated by antibodies specific for ßig-h3, and no significant differences on inhibitory effects were observed among T7721 cells incubated with antibodies for ßig-h3 or HAb18G/CD147 or both types together. Taken together, our study suggests that ßig-h3, regulated by the expression of HAb18G/CD147, is involved in the HAb18G/CD147 signal transduction pathway and mediates the HAb18G/CD147-induced invasion and metastasis process of human hepatoma cells.

Key Words: HAb18G • CD147 • ßig-h3 • hepatoma cell • metastasis