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  • Title: Downregulation of glypican-3 expression increases migration, invasion, and tumorigenicity of human ovarian cancer cells.
    Author: Liu Y, Zheng D, Liu M, Bai J, Zhou X, Gong B, Lü J, Zhang Y, Huang H, Luo W, Huang G.
    Journal: Tumour Biol; 2015 Sep; 36(10):7997-8006. PubMed ID: 25967456.
    Abstract:
    Glypican-3 (GPC3) is a membrane of heparan sulfate proteoglycan family involved in cell proliferation, adhesion, migration, invasion, and differentiation during the development of the majority of mesodermal tissues and organs. GPC3 is explored as a potential biomarker for hepatocellular carcinoma screening. However, as a tumor-associated antigen, its role in ovarian cancer remains elusive. In this report, the expression levels of GPC3 in the various ovarian cancer cells were determined with quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and GPC3 expression in ovarian cancer UCI 101 and A2780 cells was knocked down by siRNA transfection, and the effects of GPC3 knockdown on in vitro cell proliferation, migration, and invasion were respectively analyzed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay and Transwell migration assay. Additionally, the effect of GPC3 knockdown on in vivo tumorigenesis were investigated in athymic nude mice. The results indicated that GPC3 knockdown significantly promoted cell proliferation and increased cell migration and invasion by upregulation of matrix metalloproteinase (MMP)-2 and MMP-9 expression and downregulation of tissue inhibitor of metalloproteinase-1 expression. Additionally, GPC3 knockdown also increased in vivo tumorigenicity of UCI 101 and A2780 cells and final tumor weights and volumes after subcutaneous cell injection in the nude mice. The results of immunohistochemical staining and Western blotting both demonstrated a lower expression of GPC3 antigen in the tumors of GPC3 knockdown groups than that of negative control groups. Moreover, transforming growth factor-β2 protein expression in the tumors of GPC3 knockdown groups was significantly increased, which at least contributed to tumor growth in the nude mice. Taken together, these findings suggest that GPC3 knockdown promotes the progression of human ovarian cancer cells by increasing their migration, invasion, and tumorigenicity, and suggest that GPC3 is a potential therapeutic target for ovarian cancer patients.
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