Cargando…
Chloride intracellular channel protein 2 in cancer and non-cancer human tissues: relationship with tight junctions
Chloride intracellular channel protein 2 (CLIC2) belongs to the CLIC family of conserved metazoan proteins. Although CLICs have been identified as chloride channels, they are currently considered multifunctional proteins. CLIC2 is the least studied family member. We investigated CLIC2 expression and...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592591/ https://www.ncbi.nlm.nih.gov/pubmed/30929599 http://dx.doi.org/10.1080/21688370.2019.1593775 |
_version_ | 1783429914225016832 |
---|---|
author | Ueno, Yoshitomo Ozaki, Saya Umakoshi, Akihiro Yano, Hajime Choudhury, Mohammed E. Abe, Naoki Sumida, Yutaro Kuwabara, Jun Uchida, Rina Islam, Afsana Ogawa, Kohei Ishimaru, Kei Yorozuya, Toshihiro Kunieda, Takeharu Watanabe, Yuji Takada, Yasutsugu Tanaka, Junya |
author_facet | Ueno, Yoshitomo Ozaki, Saya Umakoshi, Akihiro Yano, Hajime Choudhury, Mohammed E. Abe, Naoki Sumida, Yutaro Kuwabara, Jun Uchida, Rina Islam, Afsana Ogawa, Kohei Ishimaru, Kei Yorozuya, Toshihiro Kunieda, Takeharu Watanabe, Yuji Takada, Yasutsugu Tanaka, Junya |
author_sort | Ueno, Yoshitomo |
collection | PubMed |
description | Chloride intracellular channel protein 2 (CLIC2) belongs to the CLIC family of conserved metazoan proteins. Although CLICs have been identified as chloride channels, they are currently considered multifunctional proteins. CLIC2 is the least studied family member. We investigated CLIC2 expression and localization in human hepatocellular carcinoma, metastatic colorectal cancer in the liver, and colorectal cancer. Significant expression of mRNAs encoding CLIC1, 2, 4, and 5 were found in the human tissues, but only CLIC2 was predominantly expressed in non-cancer tissues surrounding cancer masses. Fibrotic or dysfunctional (aspartate aminotransferase ≥40) non-cancer liver tissues and advanced stage HCC tissues expressed low levels of CLIC2. Endothelial cells lining blood vessels but not lymphatic vessels in non-cancer tissues expressed CLIC2 as well as high levels of the tight junction proteins claudins 1 and 5, occludin, and ZO-1. Most endothelial cells in blood vessels in cancer tissues had very low expressions of CLIC2 and tight junction proteins. CD31(+)/CD45(−) endothelial cells isolated from non-cancer tissues expressed mRNAs encoding CLIC2, claudin 1, occludin and ZO-1, while similar cell fractions from cancer tissues had very low expressions of these molecules. Knockdown of CLIC2 expression in human umbilical vein endothelial cells (HUVECs) allowed human cancer cells to transmigrate through a HUVEC monolayer. These results suggest that CLIC2 may be involved in the formation and/or maintenance of tight junctions and that cancer tissue vasculature lacks CLIC2 and tight junctions, which allows the intravasation of cancer cells necessary for hematogenous metastasis. |
format | Online Article Text |
id | pubmed-6592591 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-65925912019-07-01 Chloride intracellular channel protein 2 in cancer and non-cancer human tissues: relationship with tight junctions Ueno, Yoshitomo Ozaki, Saya Umakoshi, Akihiro Yano, Hajime Choudhury, Mohammed E. Abe, Naoki Sumida, Yutaro Kuwabara, Jun Uchida, Rina Islam, Afsana Ogawa, Kohei Ishimaru, Kei Yorozuya, Toshihiro Kunieda, Takeharu Watanabe, Yuji Takada, Yasutsugu Tanaka, Junya Tissue Barriers Research Paper Chloride intracellular channel protein 2 (CLIC2) belongs to the CLIC family of conserved metazoan proteins. Although CLICs have been identified as chloride channels, they are currently considered multifunctional proteins. CLIC2 is the least studied family member. We investigated CLIC2 expression and localization in human hepatocellular carcinoma, metastatic colorectal cancer in the liver, and colorectal cancer. Significant expression of mRNAs encoding CLIC1, 2, 4, and 5 were found in the human tissues, but only CLIC2 was predominantly expressed in non-cancer tissues surrounding cancer masses. Fibrotic or dysfunctional (aspartate aminotransferase ≥40) non-cancer liver tissues and advanced stage HCC tissues expressed low levels of CLIC2. Endothelial cells lining blood vessels but not lymphatic vessels in non-cancer tissues expressed CLIC2 as well as high levels of the tight junction proteins claudins 1 and 5, occludin, and ZO-1. Most endothelial cells in blood vessels in cancer tissues had very low expressions of CLIC2 and tight junction proteins. CD31(+)/CD45(−) endothelial cells isolated from non-cancer tissues expressed mRNAs encoding CLIC2, claudin 1, occludin and ZO-1, while similar cell fractions from cancer tissues had very low expressions of these molecules. Knockdown of CLIC2 expression in human umbilical vein endothelial cells (HUVECs) allowed human cancer cells to transmigrate through a HUVEC monolayer. These results suggest that CLIC2 may be involved in the formation and/or maintenance of tight junctions and that cancer tissue vasculature lacks CLIC2 and tight junctions, which allows the intravasation of cancer cells necessary for hematogenous metastasis. Taylor & Francis 2019-03-31 /pmc/articles/PMC6592591/ /pubmed/30929599 http://dx.doi.org/10.1080/21688370.2019.1593775 Text en © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
spellingShingle | Research Paper Ueno, Yoshitomo Ozaki, Saya Umakoshi, Akihiro Yano, Hajime Choudhury, Mohammed E. Abe, Naoki Sumida, Yutaro Kuwabara, Jun Uchida, Rina Islam, Afsana Ogawa, Kohei Ishimaru, Kei Yorozuya, Toshihiro Kunieda, Takeharu Watanabe, Yuji Takada, Yasutsugu Tanaka, Junya Chloride intracellular channel protein 2 in cancer and non-cancer human tissues: relationship with tight junctions |
title | Chloride intracellular channel protein 2 in cancer and non-cancer human tissues: relationship with tight junctions |
title_full | Chloride intracellular channel protein 2 in cancer and non-cancer human tissues: relationship with tight junctions |
title_fullStr | Chloride intracellular channel protein 2 in cancer and non-cancer human tissues: relationship with tight junctions |
title_full_unstemmed | Chloride intracellular channel protein 2 in cancer and non-cancer human tissues: relationship with tight junctions |
title_short | Chloride intracellular channel protein 2 in cancer and non-cancer human tissues: relationship with tight junctions |
title_sort | chloride intracellular channel protein 2 in cancer and non-cancer human tissues: relationship with tight junctions |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592591/ https://www.ncbi.nlm.nih.gov/pubmed/30929599 http://dx.doi.org/10.1080/21688370.2019.1593775 |
work_keys_str_mv | AT uenoyoshitomo chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions AT ozakisaya chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions AT umakoshiakihiro chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions AT yanohajime chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions AT choudhurymohammede chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions AT abenaoki chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions AT sumidayutaro chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions AT kuwabarajun chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions AT uchidarina chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions AT islamafsana chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions AT ogawakohei chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions AT ishimarukei chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions AT yorozuyatoshihiro chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions AT kuniedatakeharu chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions AT watanabeyuji chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions AT takadayasutsugu chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions AT tanakajunya chlorideintracellularchannelprotein2incancerandnoncancerhumantissuesrelationshipwithtightjunctions |