Role of organic cation transporter 3 (OCT3) in the response of hepatocellular carcinoma to tyrosine kinase inhibitors
Impaired function of organic cation transporter 1 (OCT1) in hepatocellular carcinoma (HCC) has been associated with unsatisfactory response to sorafenib. However, some patients lacking OCT1 at the plasma membrane (PM) of HCC cells still respond to sorafenib, suggesting that another transporter may c...
| Autores: | , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad de Salamanca (USAL) |
| Repositorio: | GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| OAI Identifier: | oai:gredos.usal.es:10366/155300 |
| Acceso en línea: | http://hdl.handle.net/10366/155300 |
| Access Level: | acceso abierto |
| Palabra clave: | Hepatocarcinoma Chemoresistance Biomarker Membrane Transport Proteins Liver Neoplasms Carcinoma Humans 3209 Farmacología neoplasias hepáticas humanos carcinoma proteínas de transporte de membrana |
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Role of organic cation transporter 3 (OCT3) in the response of hepatocellular carcinoma to tyrosine kinase inhibitorsHerráez Aguilar, ElisaAl Abdulla, RubaSoto Muñiz, MerarisBriz Sánchez, OscarBettinger, DominikBantel, HeikeCarmen Martínez, Sofía delSerrano García, María ÁngelesGeier, AndreasGarcía Marín, José JuanRodríguez Macías, Rocío IsabelHepatocarcinomaChemoresistanceBiomarkerMembrane Transport ProteinsLiver NeoplasmsCarcinomaHumans3209 Farmacologíaneoplasias hepáticashumanoscarcinomaproteínas de transporte de membranaImpaired function of organic cation transporter 1 (OCT1) in hepatocellular carcinoma (HCC) has been associated with unsatisfactory response to sorafenib. However, some patients lacking OCT1 at the plasma membrane (PM) of HCC cells still respond to sorafenib, suggesting that another transporter may contribute to take up this drug. The aim of this study was to investigate whether OCT3 could contribute to the uptake of sorafenib and other tyrosine kinase inhibitors (TKIs) and whether OCT3 determination can predict HCC response to sorafenib. Cells overexpressing OCT3 were used to determine the ability of this carrier to transport sorafenib. Immunostaining of OCT3 was performed in HCC samples obtained in the TRANSFER study. Considering the intensity of staining and the number of OCT3-positive cells, tumors were classified as having absent, weak, moderate, or strong OCT3 expression and were also categorized according to the presence or absence of PM staining. Functional in vitro studies revealed that OCT3 is also able to mediate sorafenib uptake. Other TKIs, such as regorafenib, lenvatinib, and cabozantinib can also interact with this transporter. In silico studies suggested that the expression of OCT3 is better preserved in HCC than that of OCT1. In HCC samples, OCT3 was expressed at the PM of cancer cells, and its presence, detected in 26% of tumors, was associated with better outcomes in patients treated with sorafenib. In conclusion, analysis by immunohistochemistry of OCT3 in the PM of tumor cells may help to predict the response of HCC patients to sorafenib and potentially to other TKIs.Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III Junta de Castilla y Leon202420242023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10366/155300reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)InglésPI19/00819PI20/00189PI22/00526SA074P20GRS 2322/A/21info:eu-repo/semantics/openAccessoai:gredos.usal.es:10366/1553002026-06-07T06:28:51Z |
| dc.title.none.fl_str_mv |
Role of organic cation transporter 3 (OCT3) in the response of hepatocellular carcinoma to tyrosine kinase inhibitors |
| title |
Role of organic cation transporter 3 (OCT3) in the response of hepatocellular carcinoma to tyrosine kinase inhibitors |
| spellingShingle |
Role of organic cation transporter 3 (OCT3) in the response of hepatocellular carcinoma to tyrosine kinase inhibitors Herráez Aguilar, Elisa Hepatocarcinoma Chemoresistance Biomarker Membrane Transport Proteins Liver Neoplasms Carcinoma Humans 3209 Farmacología neoplasias hepáticas humanos carcinoma proteínas de transporte de membrana |
| title_short |
Role of organic cation transporter 3 (OCT3) in the response of hepatocellular carcinoma to tyrosine kinase inhibitors |
| title_full |
Role of organic cation transporter 3 (OCT3) in the response of hepatocellular carcinoma to tyrosine kinase inhibitors |
| title_fullStr |
Role of organic cation transporter 3 (OCT3) in the response of hepatocellular carcinoma to tyrosine kinase inhibitors |
| title_full_unstemmed |
Role of organic cation transporter 3 (OCT3) in the response of hepatocellular carcinoma to tyrosine kinase inhibitors |
| title_sort |
Role of organic cation transporter 3 (OCT3) in the response of hepatocellular carcinoma to tyrosine kinase inhibitors |
| dc.creator.none.fl_str_mv |
Herráez Aguilar, Elisa Al Abdulla, Ruba Soto Muñiz, Meraris Briz Sánchez, Oscar Bettinger, Dominik Bantel, Heike Carmen Martínez, Sofía del Serrano García, María Ángeles Geier, Andreas García Marín, José Juan Rodríguez Macías, Rocío Isabel |
| author |
Herráez Aguilar, Elisa |
| author_facet |
Herráez Aguilar, Elisa Al Abdulla, Ruba Soto Muñiz, Meraris Briz Sánchez, Oscar Bettinger, Dominik Bantel, Heike Carmen Martínez, Sofía del Serrano García, María Ángeles Geier, Andreas García Marín, José Juan Rodríguez Macías, Rocío Isabel |
| author_role |
author |
| author2 |
Al Abdulla, Ruba Soto Muñiz, Meraris Briz Sánchez, Oscar Bettinger, Dominik Bantel, Heike Carmen Martínez, Sofía del Serrano García, María Ángeles Geier, Andreas García Marín, José Juan Rodríguez Macías, Rocío Isabel |
| author2_role |
author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Hepatocarcinoma Chemoresistance Biomarker Membrane Transport Proteins Liver Neoplasms Carcinoma Humans 3209 Farmacología neoplasias hepáticas humanos carcinoma proteínas de transporte de membrana |
| topic |
Hepatocarcinoma Chemoresistance Biomarker Membrane Transport Proteins Liver Neoplasms Carcinoma Humans 3209 Farmacología neoplasias hepáticas humanos carcinoma proteínas de transporte de membrana |
| description |
Impaired function of organic cation transporter 1 (OCT1) in hepatocellular carcinoma (HCC) has been associated with unsatisfactory response to sorafenib. However, some patients lacking OCT1 at the plasma membrane (PM) of HCC cells still respond to sorafenib, suggesting that another transporter may contribute to take up this drug. The aim of this study was to investigate whether OCT3 could contribute to the uptake of sorafenib and other tyrosine kinase inhibitors (TKIs) and whether OCT3 determination can predict HCC response to sorafenib. Cells overexpressing OCT3 were used to determine the ability of this carrier to transport sorafenib. Immunostaining of OCT3 was performed in HCC samples obtained in the TRANSFER study. Considering the intensity of staining and the number of OCT3-positive cells, tumors were classified as having absent, weak, moderate, or strong OCT3 expression and were also categorized according to the presence or absence of PM staining. Functional in vitro studies revealed that OCT3 is also able to mediate sorafenib uptake. Other TKIs, such as regorafenib, lenvatinib, and cabozantinib can also interact with this transporter. In silico studies suggested that the expression of OCT3 is better preserved in HCC than that of OCT1. In HCC samples, OCT3 was expressed at the PM of cancer cells, and its presence, detected in 26% of tumors, was associated with better outcomes in patients treated with sorafenib. In conclusion, analysis by immunohistochemistry of OCT3 in the PM of tumor cells may help to predict the response of HCC patients to sorafenib and potentially to other TKIs. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023 2024 2024 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10366/155300 |
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http://hdl.handle.net/10366/155300 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
PI19/00819 PI20/00189 PI22/00526 SA074P20 GRS 2322/A/21 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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reponame:GREDOS. Repositorio Institucional de la Universidad de Salamanca instname:Universidad de Salamanca (USAL) |
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Universidad de Salamanca (USAL) |
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GREDOS. Repositorio Institucional de la Universidad de Salamanca |
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GREDOS. Repositorio Institucional de la Universidad de Salamanca |
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15.301603 |