871 EXTRACELLULAR MATRIX METALLOPROTEINASE INDUCER (EMMPRIN/CD147) IS ASSOCIATED WITH MALIGNANT PHENOTYPES OF HUMAN BLADDER CANCER

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INTRODUCTION AND OBJECTIVES: Extracellular matrix metalloproteinase inducer (EMMPRIN or CD147), a member of the immunoglobulin superfamily, is a glycoprotein present on the cell surface of tumor cells that promotes invasion, metastasis, growth, and resistance to apoptosis. CD147 stimulates matrix metalloproteinase (MMP) production not only in tumor cells but also in normal peripheral cells, such as stromal fibroblasts, through tumor–stromal cell contact. In this study, we investigated the function of CD147 in human bladder cancer cell lines and its clinical relevance in human bladder cancer. METHODS: Western blot analysis and immunocytochemistry were employed to evaluate CD147 expression in normal human fibroblasts and in the human bladder cancer cell lines 5637, UMUC3, TCCSUP, KU7, and RT4 (a bladder papilloma cell line). Silencing of CD147 expression was performed using siRNA oligonucleotides, and functional consequences were assessed using invasion assay, wound healing migration assay, proliferation assay, MMP-2, and MMP-9 ELISA. Apoptosis induction was detected using cleaved PARP and active caspase-3 on Western blot analysis. CD147 expression patterns in totally extirpated human bladder cancer tissues obtained by radical cystectomy were examined by immunohistochemistry. In order to determine the prognostic value of CD147, overall survival and progression-free survival were evaluated using the Kaplan–Meier method. RESULTS: CD147 was highly expressed on the cell surface in all bladder cancer cell lines. siRNA-induced CD147 downregulation resulted in reduction of MMP-2 and MMP-9 production; inhibition of invasion, migration, and proliferation; and stimulation of apoptosis. EMMPRIN/CD147 expression levels in bladder cancer tissues were significantly associated with the overall survival in patients who underwent radical cystectomy. CONCLUSIONS: The results suggest that CD147, which is highly expressed in human bladder cancer cell lines and bladder cancer in vivo, plays significant roles in association with the malignant phenotypes in bladder cancer in vivo and in vitro. CD147 may be used as a potential target of drugs for bladder cancer patients.