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LIVER AND BILIARY TRACT

Trail induces cell migration and invasion in apoptosis-resistant cholangiocarcinoma cells

Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota

Submitted 25 May 2005 ; accepted in final form 23 August 2005

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for cancer therapy; however, many cholangiocarcinoma cells are resistant to TRAIL-mediated apoptosis. Resistance to apoptosis may unmask TRAIL signaling cascades favoring tumor biology. Thus our aim was to examine whether TRAIL is expressed by human cholangiocarcinomas, and if so, to determine whether it promotes a malignant phenotype. To address this objective, TRAIL expression in human liver specimens was evaluated by immunohistochemistry. The effect of TRAIL on tumor cell migration, invasion, and proliferation was examined in three human cholangiocarcinoma cell lines. TRAIL expression was upregulated by cholangiocytes in preneoplastic disease, primary sclerosing cholangitis, and human cholangiocarcinoma specimens. TRAIL promoted tumor cell migration and invasion but did not induce cell proliferation. TRAIL-mediated cell migration and invasion was NF-B dependent. These data demonstrate that TRAIL promotes cell migration and invasion via a NF-B-dependent pathway in human cholangiocarcinoma cell lines, an observation that has a potential negative implication for TRAIL in cancer therapy.

cholangiocyte; tumor necrosis factor-related apoptosis-inducing ligand; nuclear factor-B; malignant phenotype

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