Anti-Cadherin-17 Antibody Modulates Beta-Catenin Signaling and Tumorigenicity of Hepatocellular Carcinoma
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{"title"=>"Anti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of hepatocellular carcinoma", "type"=>"journal", "authors"=>[{"first_name"=>"Yonggang", "last_name"=>"Wang", "scopus_author_id"=>"54881352700"}, {"first_name"=>"Felix H.", "last_name"=>"Shek", "scopus_author_id"=>"36094922800"}, {"first_name"=>"Kwong F.", "last_name"=>"Wong", "scopus_author_id"=>"56150844900"}, {"first_name"=>"Ling Xiao", "last_name"=>"Liu", "scopus_author_id"=>"13611939300"}, {"first_name"=>"Xiao Qian", "last_name"=>"Zhang", "scopus_author_id"=>"35791324600"}, {"first_name"=>"Yi", "last_name"=>"Yuan", "scopus_author_id"=>"56197493100"}, {"first_name"=>"Ester", "last_name"=>"Khin", "scopus_author_id"=>"23008725600"}, {"first_name"=>"Mei Yu", "last_name"=>"Hu", "scopus_author_id"=>"7402639252"}, {"first_name"=>"Jian Hua", "last_name"=>"Wang", "scopus_author_id"=>"56023470000"}, {"first_name"=>"Ronnie T.P.", "last_name"=>"Poon", "scopus_author_id"=>"7103097223"}, {"first_name"=>"Wanjin", "last_name"=>"Hong", "scopus_author_id"=>"57196221684"}, {"first_name"=>"Nikki P.", "last_name"=>"Lee", "scopus_author_id"=>"7402722690"}, {"first_name"=>"John M.", "last_name"=>"Luk", "scopus_author_id"=>"7006777791"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"618924342", "doi"=>"10.1371/journal.pone.0072386", "isbn"=>"1932-6203", "pmid"=>"24039755", "issn"=>"19326203", "scopus"=>"2-s2.0-84902030237", "sgr"=>"84902030237"}, "id"=>"718b2db5-293c-3091-90d2-9519365b83bb", "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 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.", "link"=>"http://www.mendeley.com/research/anticadherin17-antibody-modulates-betacatenin-signaling-tumorigenicity-hepatocellular-carcinoma", "reader_count"=>11, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>2, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>2, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>5, "Neuroscience"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1201589", "https://ndownloader.figshare.com/files/1201590", "https://ndownloader.figshare.com/files/1201591"], "description"=>"<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>", "links"=>[], "tags"=>["antibody", "modulates", "beta-catenin", "tumorigenicity", "hepatocellular"], "article_id"=>797341, "categories"=>["Biological Sciences"], "users"=>["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"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0072386.s001", "https://dx.doi.org/10.1371/journal.pone.0072386.s002", "https://dx.doi.org/10.1371/journal.pone.0072386.s003"], "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Anti_Cadherin_17_Antibody_Modulates_Beta_Catenin_Signaling_and_Tumorigenicity_of_Hepatocellular_Carcinoma_/797341", "title"=>"Anti-Cadherin-17 Antibody Modulates Beta-Catenin Signaling and Tumorigenicity of Hepatocellular Carcinoma", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-09-11 02:41:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1201582"], "description"=>"<p>Treatment of tumor-bearing nude mice with Lic5 inhibits tumor growth and sensitizes tumors to cisplatin. HCC subcutaneous tumors were developed in nude mice using CDH17-expressing MHCC97L cells. Tumor-bearing nude mice were then injected with Lic5 alone, 2.5 mg/kg (Lic5_L) or 5 mg/kg (Lic5_H), or in combination of 1 mg/kg cisplatin (Lic+cis).Mice of the control group received mouse IgG (5 mg/kg). All mice were injected three times weekly for four consecutive weeks. (A) Sizes of the subcutaneous tumors were estimated weekly throughout the experimental period (left panel) and subcutaneous tumors were resected 28 days after the onset of treatment (right panel). Reduction in the sizes of the tumors was observed in single treatment group (Lic5 or cisplatin). Combined regimen of Lic5 and cisplatin (Lic+cis) could result a complete inhibition on tumor growth. All <i>p</i>-values were calculated using Student's <i>t</i>-test of GraphPad PRISM, for which 6 tumor samples were included in each group for comparison between control and treatment groups. *, <i>p</i><0.05 and ***, <i>p</i><0.001. (B) The level of proliferating cells in HCC xenografts was studied using immunohistochemistry. A significant reduction in the number of Ki67-stained cells was observed in xenografts of mice injected Lic5, alone and in combination with cisplatin. Original magnification, ×400; scale bar, 80 µm. *, <i>p</i><0.01 and **, <i>p</i><0.001. (C) Lic5 treatment of tumor-bearing nude mice decreases the chance of developing metastatic tumors in lungs. Any tumors grew in lungs were spotted by staining with hematoxylin and eosin in series of sections derived from lung specimens. Treatment of these mice using Lic5 reduced the percentage of mice having metastatic tumors in lungs and the most significant effect was observed in combined treatment group with Lic5 and cisplatin. Chi-squared test was applied to compare control group with all other groups. *, <i>p</i><0.05. Original magnification, ×400; scale bar, 40 µm.</p>", "links"=>[], "tags"=>["anti-metastatic", "lic5", "mhcc97l", "xenograft"], "article_id"=>797334, "categories"=>["Biological Sciences"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0072386.g002", "stats"=>{"downloads"=>2, "page_views"=>103, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Antitumor_and_anti_metastatic_properties_of_Lic5_in_MHCC97L_xenograft_mouse_model_/797334", "title"=>"Antitumor and anti-metastatic properties of Lic5 in MHCC97L xenograft mouse model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-11 02:41:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1201571"], "description"=>"<p>Treatment of HCC cells with Lic5 inactivated CDH17/β-catenin signaling pathway and induced apoptosis. (A) MHCC97L cells with high level of CDH17 were treated with an increasing concentration of Lic5 from 25 to 200 µg/mL. A dose-dependent reduction in the protein level of CDH17 was detected using western blot. (B) Confocal microscopy images showed a reduction in cellular levels of total and phospho-β-catenin (at Thr41 and Ser45) proteins after Lic5 treatment in MHCC97H cells. PBS was used as a negative control. Scale bar, 20 µm. (C) Real-time qPCR showed a time-dependent reduction of cyclin D1 gene expression level in MHCC97H cells after treatment with Lic5 for 18, 36 and 48 hours.*, <i>p</i> = 0.001493; **, <i>p</i> = 0.00001424; ***, <i>p</i> = 0.00001377, when compared to the Mock (PBS) or IgG control. Shown are the representative set of data of three independent experiments, with each column represents the mean values of triplicate data. All <i>p</i>-values were calculated using ANOVA test of GraphPad PRISM. (D) Western blots showed treatment with Lic5 induced cleavage of caspase-8 and -9, but not by the Mock and IgG controls.</p>", "links"=>[], "tags"=>["experiments", "treating", "metastatic", "hcc", "cells"], "article_id"=>797332, "categories"=>["Biological Sciences"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0072386.g001", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vitro_experiments_of_treating_metastatic_HCC_cells_with_Lic5_/797332", "title"=>"<i>In vitro</i> experiments of treating metastatic HCC cells with Lic5.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-11 02:41:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1201585"], "description"=>"<p>Mice having MHCC97L-derived tumors were subjected to single or combined treatment of Lic5 and cisplatin as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072386#pone-0072386-g002\" target=\"_blank\">Fig. 2</a>. (A) Changes in the protein level of Wnt/β-catenin pathway components like β-catenin, cyclin D1 and retinoblastoma (Rb) in resected HCC tumors were detected using western blot. Suppression of CDH17 level using Lic5 accompanied with an inactivation of Wnt/β-catenin pathway, leading to reduction in the levels of β-catenin and cyclin D1 and induction in the level of Rb. β-Actin was used as a loading control. (B) Similar trend in the changes of the levels of β-catenin, cyclin D1 and Rb was observed in tissue sections of the HCC tumor xenografts using immunohistochemistry. Original magnification, ×400; scale bar, 80 µm.</p>", "links"=>[], "tags"=>["inactivated", "hcc"], "article_id"=>797337, "categories"=>["Biological Sciences"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0072386.g003", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lic5_treatment_inactivated_Wnt_946_catenin_signaling_in_HCC_tumors_/797337", "title"=>"Lic5 treatment inactivated Wnt/β-catenin signaling in HCC tumors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-11 02:41:15"}

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Relative Metric

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