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STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma
Interleukin (IL)-22 is a member of the IL-10 family. Its main targets are epithelial cells, not immune cells. We examined IL-22 signal transduction in oral squamous cell carcinoma (OSCC) cells. Immunohistochemical staining revealed that IL-22R was expressed more highly in OSCC compared to normal reg...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583669/ https://www.ncbi.nlm.nih.gov/pubmed/22922995 http://dx.doi.org/10.3892/ijo.2012.1594 |
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author | NAHER, LUTFUN KIYOSHIMA, TAMOTSU KOBAYASHI, IEYOSHI WADA, HIROKO NAGATA, KENGO FUJIWARA, HIROAKI OOKUMA, YUKIKO F. OZEKI, SATORU NAKAMURA, SEIJI SAKAI, HIDETAKA |
author_facet | NAHER, LUTFUN KIYOSHIMA, TAMOTSU KOBAYASHI, IEYOSHI WADA, HIROKO NAGATA, KENGO FUJIWARA, HIROAKI OOKUMA, YUKIKO F. OZEKI, SATORU NAKAMURA, SEIJI SAKAI, HIDETAKA |
author_sort | NAHER, LUTFUN |
collection | PubMed |
description | Interleukin (IL)-22 is a member of the IL-10 family. Its main targets are epithelial cells, not immune cells. We examined IL-22 signal transduction in oral squamous cell carcinoma (OSCC) cells. Immunohistochemical staining revealed that IL-22R was expressed more highly in OSCC compared to normal regions. An IL-22R signal was also observed in metastatic OSCC cells in the lymph node. RT-PCR showed that the human OSCC cell lines MISK81-5, HSC-3, HSC-4, SAS and SQUU-B expressed IL-22 receptor chains. Immunoblotting showed that IL-22 induced a transient tyrosine phosphorylation of STAT3 (pY705-STAT3) in MISK81-5 cells. The change in the serine phosphorylation of STAT3 was subtle during the examination periods. Simultaneously, pY705-STAT3 activation in HSC-3 cells was undetectable after IL-22 stimulation. Immunocytochemistry demonstrated that IL-22 induced the translocation of phosphorylated STAT3 into the nucleus of MISK81-5 cells. IL-22 temporarily upregulated the expression of anti-apoptotic and mitogenic genes such as Bcl-x, survivin and c-Myc, as well as SOCS3. IL-22 transiently activated ERK1/2 and induced a delayed phosphorylation of p38 MAP kinase, but negligibly involved the activation of NF-κB in MISK81-5 cells. MISK81-5 and SQUU-B cells treated with IL-22 showed mild cellular proliferation. MISK81-5, HSC-4 and SAS cells treated with IL-22 downregulated the keratinocyte differentiation-related genes compared with unstimulated cells. Conversely, STAT3 suppression by STAT3 siRNA strongly disrupted the down-regulation of these genes by IL-22, but it did not significantly affect the activation of ERK1/2 by IL-22. The OSCC cells used in this study upregulated the expression of SERPINB3/4 (SCCA1/2), well-known SCC markers, following treatment with IL-22. These results indicate that IL-22 differentially activates the STAT3 signaling system depending on the type of OSCC. IL-22 may therefore play a role in tumor growth, cell differentiation and progression through STAT3-dependent and -independent pathways. |
format | Online Article Text |
id | pubmed-3583669 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-35836692013-03-04 STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma NAHER, LUTFUN KIYOSHIMA, TAMOTSU KOBAYASHI, IEYOSHI WADA, HIROKO NAGATA, KENGO FUJIWARA, HIROAKI OOKUMA, YUKIKO F. OZEKI, SATORU NAKAMURA, SEIJI SAKAI, HIDETAKA Int J Oncol Articles Interleukin (IL)-22 is a member of the IL-10 family. Its main targets are epithelial cells, not immune cells. We examined IL-22 signal transduction in oral squamous cell carcinoma (OSCC) cells. Immunohistochemical staining revealed that IL-22R was expressed more highly in OSCC compared to normal regions. An IL-22R signal was also observed in metastatic OSCC cells in the lymph node. RT-PCR showed that the human OSCC cell lines MISK81-5, HSC-3, HSC-4, SAS and SQUU-B expressed IL-22 receptor chains. Immunoblotting showed that IL-22 induced a transient tyrosine phosphorylation of STAT3 (pY705-STAT3) in MISK81-5 cells. The change in the serine phosphorylation of STAT3 was subtle during the examination periods. Simultaneously, pY705-STAT3 activation in HSC-3 cells was undetectable after IL-22 stimulation. Immunocytochemistry demonstrated that IL-22 induced the translocation of phosphorylated STAT3 into the nucleus of MISK81-5 cells. IL-22 temporarily upregulated the expression of anti-apoptotic and mitogenic genes such as Bcl-x, survivin and c-Myc, as well as SOCS3. IL-22 transiently activated ERK1/2 and induced a delayed phosphorylation of p38 MAP kinase, but negligibly involved the activation of NF-κB in MISK81-5 cells. MISK81-5 and SQUU-B cells treated with IL-22 showed mild cellular proliferation. MISK81-5, HSC-4 and SAS cells treated with IL-22 downregulated the keratinocyte differentiation-related genes compared with unstimulated cells. Conversely, STAT3 suppression by STAT3 siRNA strongly disrupted the down-regulation of these genes by IL-22, but it did not significantly affect the activation of ERK1/2 by IL-22. The OSCC cells used in this study upregulated the expression of SERPINB3/4 (SCCA1/2), well-known SCC markers, following treatment with IL-22. These results indicate that IL-22 differentially activates the STAT3 signaling system depending on the type of OSCC. IL-22 may therefore play a role in tumor growth, cell differentiation and progression through STAT3-dependent and -independent pathways. D.A. Spandidos 2012-08-21 /pmc/articles/PMC3583669/ /pubmed/22922995 http://dx.doi.org/10.3892/ijo.2012.1594 Text en Copyright © 2012, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Articles NAHER, LUTFUN KIYOSHIMA, TAMOTSU KOBAYASHI, IEYOSHI WADA, HIROKO NAGATA, KENGO FUJIWARA, HIROAKI OOKUMA, YUKIKO F. OZEKI, SATORU NAKAMURA, SEIJI SAKAI, HIDETAKA STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma |
title | STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma |
title_full | STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma |
title_fullStr | STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma |
title_full_unstemmed | STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma |
title_short | STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma |
title_sort | stat3 signal transduction through interleukin-22 in oral squamous cell carcinoma |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583669/ https://www.ncbi.nlm.nih.gov/pubmed/22922995 http://dx.doi.org/10.3892/ijo.2012.1594 |
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