Differential Inhibition of the TGF-β Signaling Pathway in HCC Cells Using the Small Molecule Inhibitor LY2157299 and the D10 Monoclonal Antibody against TGF-β Receptor Type II

We investigated blocking the TGF-β signaling pathway in HCC using two small molecule inhibitors (LY2157299, LY2109761) and a neutralizing humanized antibody (D10) against TGF-βRII. LY2157299 and LY2109761 inhibited HCC cell migration on Laminin-5, Fibronectin, Vitronectin, Fibrinogen and Collagen-I...

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Autores principales: Dituri, Francesco, Mazzocca, Antonio, Peidrò, Fernando Juan, Papappicco, Patrizia, Fabregat, Isabel, De Santis, Flavia, Paradiso, Angelo, Sabbà, Carlo, Giannelli, Gianluigi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694933/
https://www.ncbi.nlm.nih.gov/pubmed/23826206
http://dx.doi.org/10.1371/journal.pone.0067109
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author Dituri, Francesco
Mazzocca, Antonio
Peidrò, Fernando Juan
Papappicco, Patrizia
Fabregat, Isabel
De Santis, Flavia
Paradiso, Angelo
Sabbà, Carlo
Giannelli, Gianluigi
author_facet Dituri, Francesco
Mazzocca, Antonio
Peidrò, Fernando Juan
Papappicco, Patrizia
Fabregat, Isabel
De Santis, Flavia
Paradiso, Angelo
Sabbà, Carlo
Giannelli, Gianluigi
author_sort Dituri, Francesco
collection PubMed
description We investigated blocking the TGF-β signaling pathway in HCC using two small molecule inhibitors (LY2157299, LY2109761) and a neutralizing humanized antibody (D10) against TGF-βRII. LY2157299 and LY2109761 inhibited HCC cell migration on Laminin-5, Fibronectin, Vitronectin, Fibrinogen and Collagen-I and de novo phosphorylation of pSMAD2. LY2157299 inhibited HCC migration and cell growth independently of the expression levels of TGF-βRII. In contrast to LY2157299, D10 showed a reduction in pSMAD2 only after a short exposure. This study supports the use of LY2157299 in clinical trials, and presents new insights into TGF-β receptor cycling in cancer cells.
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spelling pubmed-36949332013-07-03 Differential Inhibition of the TGF-β Signaling Pathway in HCC Cells Using the Small Molecule Inhibitor LY2157299 and the D10 Monoclonal Antibody against TGF-β Receptor Type II Dituri, Francesco Mazzocca, Antonio Peidrò, Fernando Juan Papappicco, Patrizia Fabregat, Isabel De Santis, Flavia Paradiso, Angelo Sabbà, Carlo Giannelli, Gianluigi PLoS One Research Article We investigated blocking the TGF-β signaling pathway in HCC using two small molecule inhibitors (LY2157299, LY2109761) and a neutralizing humanized antibody (D10) against TGF-βRII. LY2157299 and LY2109761 inhibited HCC cell migration on Laminin-5, Fibronectin, Vitronectin, Fibrinogen and Collagen-I and de novo phosphorylation of pSMAD2. LY2157299 inhibited HCC migration and cell growth independently of the expression levels of TGF-βRII. In contrast to LY2157299, D10 showed a reduction in pSMAD2 only after a short exposure. This study supports the use of LY2157299 in clinical trials, and presents new insights into TGF-β receptor cycling in cancer cells. Public Library of Science 2013-06-27 /pmc/articles/PMC3694933/ /pubmed/23826206 http://dx.doi.org/10.1371/journal.pone.0067109 Text en © 2013 Dituri et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Dituri, Francesco
Mazzocca, Antonio
Peidrò, Fernando Juan
Papappicco, Patrizia
Fabregat, Isabel
De Santis, Flavia
Paradiso, Angelo
Sabbà, Carlo
Giannelli, Gianluigi
Differential Inhibition of the TGF-β Signaling Pathway in HCC Cells Using the Small Molecule Inhibitor LY2157299 and the D10 Monoclonal Antibody against TGF-β Receptor Type II
title Differential Inhibition of the TGF-β Signaling Pathway in HCC Cells Using the Small Molecule Inhibitor LY2157299 and the D10 Monoclonal Antibody against TGF-β Receptor Type II
title_full Differential Inhibition of the TGF-β Signaling Pathway in HCC Cells Using the Small Molecule Inhibitor LY2157299 and the D10 Monoclonal Antibody against TGF-β Receptor Type II
title_fullStr Differential Inhibition of the TGF-β Signaling Pathway in HCC Cells Using the Small Molecule Inhibitor LY2157299 and the D10 Monoclonal Antibody against TGF-β Receptor Type II
title_full_unstemmed Differential Inhibition of the TGF-β Signaling Pathway in HCC Cells Using the Small Molecule Inhibitor LY2157299 and the D10 Monoclonal Antibody against TGF-β Receptor Type II
title_short Differential Inhibition of the TGF-β Signaling Pathway in HCC Cells Using the Small Molecule Inhibitor LY2157299 and the D10 Monoclonal Antibody against TGF-β Receptor Type II
title_sort differential inhibition of the tgf-β signaling pathway in hcc cells using the small molecule inhibitor ly2157299 and the d10 monoclonal antibody against tgf-β receptor type ii
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694933/
https://www.ncbi.nlm.nih.gov/pubmed/23826206
http://dx.doi.org/10.1371/journal.pone.0067109
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