Hong, W

Hu, MY

Khin, E

Lee, NPY

Liu, LX

Luk, JMC

Poon, RTP

SHEK, HP

Wang, JH

Wang, Y

Wong, KF

Yuan, Y

Zhang, XQ

PLoS ONE

PubMed

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

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

Directory of Open Access Journals

Anti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of hepatocellular carcinoma.

HKU Scholars Hub

Anti-cadherin-17 antibody modulates Beta-catenin signaling and tumorigenicity of hepatocellular carcinoma

Felix H. Shek

Kwong F. Wong

Mei-yu Hu

Ronnie T. P. Poon

Nikki P. Lee

John M. Luk

Crossref

Anti-Cadherin-17 Antibody Modulates Beta-Catenin Signaling and Tumorigenicity of Hepatocellular Carcinoma

<div><p>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>In vitro</i> 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 <i>vs</i>. 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.</p></div

Yonggang Wang (115253)

Felix H. Shek (457476)

Kwong F. Wong (204900)

Ling Xiao Liu (457477)

Xiao Qian Zhang (457478)

Yi Yuan (180239)

Ester Khin (457479)

Mei-yu Hu (457480)

Jian Hua Wang (457481)

Ronnie T. P. Poon (106644)

Wanjin Hong (5654287)

Nikki P. Lee (204901)

John M. Luk (204918)

The Francis Crick Institute

https://figshare.com/articles/_Anti_Cadherin_17_Antibody_Modulates_Beta_Catenin_Signaling_and_Tumorigenicity_of_Hepatocellular_Carcinoma_/797341

Anti-cadherin-17 antibody modulates Beta-catenin signaling and tumorigenicity of hepatocellular carcinoma

Abstract

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Directory of Open Access Journals

HKU Scholars Hub

Crossref

The Francis Crick Institute