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CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells
We investigated the functional role of CEACAM1 in a spontaneous metastasis xenograft model of human melanoma in scid mice using BRAF wildtype MeWo cells with and without RNAi mediated knockdown of CEACAM1. Tumors from the xenograft model were subjected to whole genome expression analysis and metasta...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082866/ https://www.ncbi.nlm.nih.gov/pubmed/30089785 http://dx.doi.org/10.1038/s41598-018-30338-4 |
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author | Wicklein, Daniel Otto, Benjamin Suling, Anna Elies, Eva Lüers, Georg Lange, Tobias Feldhaus, Susanne Maar, Hanna Schröder-Schwarz, Jennifer Brunner, Georg Wagener, Christoph Schumacher, Udo |
author_facet | Wicklein, Daniel Otto, Benjamin Suling, Anna Elies, Eva Lüers, Georg Lange, Tobias Feldhaus, Susanne Maar, Hanna Schröder-Schwarz, Jennifer Brunner, Georg Wagener, Christoph Schumacher, Udo |
author_sort | Wicklein, Daniel |
collection | PubMed |
description | We investigated the functional role of CEACAM1 in a spontaneous metastasis xenograft model of human melanoma in scid mice using BRAF wildtype MeWo cells with and without RNAi mediated knockdown of CEACAM1. Tumors from the xenograft model were subjected to whole genome expression analysis and metastasis was quantified histologically. Results and identified markers were verified using tissue samples of over 100 melanoma patients. Knockdown of CEACAM1 prolonged the animals’ survival by significantly reducing subcutaneous growth of MeWo tumors and spontaneous lung metastasis. Microarray analysis revealed a strong influence of CEACAM1 knockdown on the network of EMT associated genes in the xenograft tumors (e.g. downregulation of BRAF, FOSL1, NRAS and TWIST). IGFBP7 and Latexin (highest up- and downregulated expression in microarray analysis) were found to be associated with longer and shorter survival, respectively, of melanoma patients. High FOSL1 and altered TWIST1 expression were found to be correlated with shortened survival in the cohort of melanoma patients. After a stepwise selection procedure combining above markers, multivariate analysis revealed IGFBP7, Latexin and altered TWIST to be prognostic markers for death. CEACAM1 could be a target for melanoma therapy as an alternative to (or in combination with) immune checkpoint and BRAF inhibitors. |
format | Online Article Text |
id | pubmed-6082866 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60828662018-08-10 CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells Wicklein, Daniel Otto, Benjamin Suling, Anna Elies, Eva Lüers, Georg Lange, Tobias Feldhaus, Susanne Maar, Hanna Schröder-Schwarz, Jennifer Brunner, Georg Wagener, Christoph Schumacher, Udo Sci Rep Article We investigated the functional role of CEACAM1 in a spontaneous metastasis xenograft model of human melanoma in scid mice using BRAF wildtype MeWo cells with and without RNAi mediated knockdown of CEACAM1. Tumors from the xenograft model were subjected to whole genome expression analysis and metastasis was quantified histologically. Results and identified markers were verified using tissue samples of over 100 melanoma patients. Knockdown of CEACAM1 prolonged the animals’ survival by significantly reducing subcutaneous growth of MeWo tumors and spontaneous lung metastasis. Microarray analysis revealed a strong influence of CEACAM1 knockdown on the network of EMT associated genes in the xenograft tumors (e.g. downregulation of BRAF, FOSL1, NRAS and TWIST). IGFBP7 and Latexin (highest up- and downregulated expression in microarray analysis) were found to be associated with longer and shorter survival, respectively, of melanoma patients. High FOSL1 and altered TWIST1 expression were found to be correlated with shortened survival in the cohort of melanoma patients. After a stepwise selection procedure combining above markers, multivariate analysis revealed IGFBP7, Latexin and altered TWIST to be prognostic markers for death. CEACAM1 could be a target for melanoma therapy as an alternative to (or in combination with) immune checkpoint and BRAF inhibitors. Nature Publishing Group UK 2018-08-08 /pmc/articles/PMC6082866/ /pubmed/30089785 http://dx.doi.org/10.1038/s41598-018-30338-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wicklein, Daniel Otto, Benjamin Suling, Anna Elies, Eva Lüers, Georg Lange, Tobias Feldhaus, Susanne Maar, Hanna Schröder-Schwarz, Jennifer Brunner, Georg Wagener, Christoph Schumacher, Udo CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells |
title | CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells |
title_full | CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells |
title_fullStr | CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells |
title_full_unstemmed | CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells |
title_short | CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells |
title_sort | ceacam1 promotes melanoma metastasis and is involved in the regulation of the emt associated gene network in melanoma cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082866/ https://www.ncbi.nlm.nih.gov/pubmed/30089785 http://dx.doi.org/10.1038/s41598-018-30338-4 |
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