Anti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of hepatocellular carcinoma.
Cadherin-17 (CDH17) is an oncofetal molecule associated with poor prognostic outcomes of hepatocellular carcinoma (HCC), for which the treatment options are very limited. The present study investigates the therapeutic potential of a monoclonal antibody (Lic5) that targets the CDH17 antigen in HCC. I...
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doaj-541a922c573b4e4fa86211a45660f3b12020-11-25T01:18:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7238610.1371/journal.pone.0072386Anti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of hepatocellular carcinoma.Yonggang WangFelix H ShekKwong F WongLing Xiao LiuXiao Qian ZhangYi YuanEster KhinMei-Yu HuJian Hua WangRonnie T P PoonWanjin HongNikki P LeeJohn M LukCadherin-17 (CDH17) is an oncofetal molecule associated with poor prognostic outcomes of hepatocellular carcinoma (HCC), for which the treatment options are very limited. The present study investigates the therapeutic potential of a monoclonal antibody (Lic5) that targets the CDH17 antigen in HCC. In vitro experiments showed Lic5 could markedly reduce CDH17 expression in a dose-dependent manner, suppress β-catenin signaling, and induce cleavages of apoptotic enzymes caspase-8 and -9 in HCC cells. Treatment of animals in subcutaneous HCC xenograft model similarly demonstrated significant tumor growth inhibition (TGI) using Lic5 antibody alone (5 mg/kg, i.p., t.i.w.; ca.60-65% TGI vs. vehicle at day 28), or in combination with conventional chemotherapy regimen (cisplatin 1 mg/kg; ca. 85-90% TGI). Strikingly, lung metastasis was markedly suppressed by Lic5 treatments. Immunohistochemical and western blot analyses of xenograft explants revealed inactivation of the Wnt pathway and suppression of Wnt signaling components in HCC tissues. Collectively, anti-CDH17 antibody promises as an effective biologic agent for treating malignant HCC.http://europepmc.org/articles/PMC3770615?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yonggang Wang Felix H Shek Kwong F Wong Ling Xiao Liu Xiao Qian Zhang Yi Yuan Ester Khin Mei-Yu Hu Jian Hua Wang Ronnie T P Poon Wanjin Hong Nikki P Lee John M Luk |
spellingShingle |
Yonggang Wang Felix H Shek Kwong F Wong Ling Xiao Liu Xiao Qian Zhang Yi Yuan Ester Khin Mei-Yu Hu Jian Hua Wang Ronnie T P Poon Wanjin Hong Nikki P Lee John M Luk Anti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of hepatocellular carcinoma. PLoS ONE |
author_facet |
Yonggang Wang Felix H Shek Kwong F Wong Ling Xiao Liu Xiao Qian Zhang Yi Yuan Ester Khin Mei-Yu Hu Jian Hua Wang Ronnie T P Poon Wanjin Hong Nikki P Lee John M Luk |
author_sort |
Yonggang Wang |
title |
Anti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of hepatocellular carcinoma. |
title_short |
Anti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of hepatocellular carcinoma. |
title_full |
Anti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of hepatocellular carcinoma. |
title_fullStr |
Anti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of hepatocellular carcinoma. |
title_full_unstemmed |
Anti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of hepatocellular carcinoma. |
title_sort |
anti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of hepatocellular carcinoma. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Cadherin-17 (CDH17) is an oncofetal molecule associated with poor prognostic outcomes of hepatocellular carcinoma (HCC), for which the treatment options are very limited. The present study investigates the therapeutic potential of a monoclonal antibody (Lic5) that targets the CDH17 antigen in HCC. In vitro experiments showed Lic5 could markedly reduce CDH17 expression in a dose-dependent manner, suppress β-catenin signaling, and induce cleavages of apoptotic enzymes caspase-8 and -9 in HCC cells. Treatment of animals in subcutaneous HCC xenograft model similarly demonstrated significant tumor growth inhibition (TGI) using Lic5 antibody alone (5 mg/kg, i.p., t.i.w.; ca.60-65% TGI vs. vehicle at day 28), or in combination with conventional chemotherapy regimen (cisplatin 1 mg/kg; ca. 85-90% TGI). Strikingly, lung metastasis was markedly suppressed by Lic5 treatments. Immunohistochemical and western blot analyses of xenograft explants revealed inactivation of the Wnt pathway and suppression of Wnt signaling components in HCC tissues. Collectively, anti-CDH17 antibody promises as an effective biologic agent for treating malignant HCC. |
url |
http://europepmc.org/articles/PMC3770615?pdf=render |
work_keys_str_mv |
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