Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0072386
Title: Anti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of hepatocellular carcinoma
Authors: Wang Y.
Shek F.H.
Wong K.F.
Liu L.X.
Zhang X.Q.
Yuan Y.
Khin E.
Hu M.-Y.
Wang J.H.
Poon R.T.P.
Hong W. 
Lee N.P.
Luk J.M.
Keywords: antineoplastic agent
beta catenin
cadherin
cadherin 17
cadherin 17 antibody
caspase 8
caspase 9
cisplatin
Lic5 antibody
monoclonal antibody
protein antibody
unclassified drug
Wnt protein
antineoplastic agent
beta catenin
cadherin
CASP8 protein, human
CASP9 protein, human
caspase 8
caspase 9
CDH17 protein, human
CTNNB1 protein, human
monoclonal antibody
animal cell
animal experiment
animal model
animal tissue
antigen expression
apoptosis
Article
beta catenin signaling
cancer combination chemotherapy
cancer inhibition
cancer model
cancer tissue
carcinogenicity
carcinoma cell
concentration response
controlled study
drug targeting
human
human cell
immunohistochemistry
in vitro study
liver cell carcinoma
lung metastasis
mouse
nonhuman
protein cleavage
randomized controlled trial
subcutaneous tissue tumor
synaptic transmission
tumor xenograft
Western blotting
Wnt signaling
animal
article
Bagg albino mouse
carcinogenesis
drug effect
drug screening
immunology
liver tumor
metabolism
tumor cell line
tumor volume
Wnt signaling pathway
Animals
Antibodies, Monoclonal
Antineoplastic Agents
beta Catenin
Cadherins
Carcinogenesis
Carcinoma, Hepatocellular
Caspase 8
Caspase 9
Cell Line, Tumor
Humans
Liver Neoplasms
Mice
Mice, Inbred BALB C
Tumor Burden
Wnt Signaling Pathway
Xenograft Model Antitumor Assays
Issue Date: 2013
Citation: Wang Y., Shek F.H., Wong K.F., Liu L.X., Zhang X.Q., Yuan Y., Khin E., Hu M.-Y., Wang J.H., Poon R.T.P., Hong W., Lee N.P., Luk J.M. (2013). Anti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of hepatocellular carcinoma. PLoS ONE 8 (9) : e72386. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0072386
Rights: Attribution 4.0 International
Abstract: 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 b-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. © 2013 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161467
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0072386
Rights: Attribution 4.0 International
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This item is licensed under a Creative Commons License Creative Commons