S100A4 Is a Strong Negative Prognostic Marker and Potential Therapeutic Target in Adenocarcinoma of the Stomach and Esophagus
Deregulated Wnt-signaling is a key mechanism driving metastasis in adenocarcinoma of the gastroesophageal junction and stomach (AGE/S). The oncogene <i>S100A4</i> was identified as a Wnt-signaling target gene and is known to promote metastasis. In this project, we illuminate the role of...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/6/1056 |
| _version_ | 1827649583777316864 |
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| author | Christoph Treese Kimberly Hartl Michelle Pötzsch Matthias Dahlmann Moritz von Winterfeld Erika Berg Michael Hummel Lena Timm Beate Rau Wolfgang Walther Severin Daum Dennis Kobelt Ulrike Stein |
| author_facet | Christoph Treese Kimberly Hartl Michelle Pötzsch Matthias Dahlmann Moritz von Winterfeld Erika Berg Michael Hummel Lena Timm Beate Rau Wolfgang Walther Severin Daum Dennis Kobelt Ulrike Stein |
| author_sort | Christoph Treese |
| collection | DOAJ |
| description | Deregulated Wnt-signaling is a key mechanism driving metastasis in adenocarcinoma of the gastroesophageal junction and stomach (AGE/S). The oncogene <i>S100A4</i> was identified as a Wnt-signaling target gene and is known to promote metastasis. In this project, we illuminate the role of S100A4 for metastases development and disease prognosis of AGE/S. Five gastric cancer cell lines were assessed for S100A4 expression. Two cell lines with endogenous high S100A4 expression were used for functional phenotyping including analysis of proliferation and migration after stable <i>S100A4</i> knock-down. The prognostic value of S100A4 was evaluated by analyzing the S100A4 expression of tissue microarrays with samples of 277 patients with AGE/S. <i>S100A4</i> knock-down induced lower migration in FLO1 and NCI-N87 cells. Treatment with niclosamide in these cells led to partial inhibition of S100A4 and to reduced migration. Patients with high S100A4 expression showed lower 5-year overall and disease-specific survival. In addition, a larger share of patients in the S100A4 high expressing group suffered from metachronous metastasis. This study identifies S100A4 as a negative prognostic marker for patients with AGE/S. The strong correlation between S100A4 expression, metastases development and patient survival might open opportunities to use S100A4 to improve the prognosis of these patients and as a therapeutic target for intervention in this tumor entity. |
| first_indexed | 2024-03-09T20:00:46Z |
| format | Article |
| id | doaj.art-372e36caa29a4d2c8a4fedb5a464787a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:00:46Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-372e36caa29a4d2c8a4fedb5a464787a2023-11-24T00:45:14ZengMDPI AGCells2073-44092022-03-01116105610.3390/cells11061056S100A4 Is a Strong Negative Prognostic Marker and Potential Therapeutic Target in Adenocarcinoma of the Stomach and EsophagusChristoph Treese0Kimberly Hartl1Michelle Pötzsch2Matthias Dahlmann3Moritz von Winterfeld4Erika Berg5Michael Hummel6Lena Timm7Beate Rau8Wolfgang Walther9Severin Daum10Dennis Kobelt11Ulrike Stein12Experimental and Clinical Research Center, Charité-Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, GermanyExperimental and Clinical Research Center, Charité-Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, GermanyDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, GermanyExperimental and Clinical Research Center, Charité-Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, GermanyInstitute of Pathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, GermanyInstitute of Pathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, GermanyInstitute of Pathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, GermanyDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, GermanyDepartment of Surgery, Campus Virchow-Klinikum and Campus Mitte, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, GermanyExperimental and Clinical Research Center, Charité-Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, GermanyDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, GermanyExperimental and Clinical Research Center, Charité-Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, GermanyExperimental and Clinical Research Center, Charité-Universitätsmedizin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, GermanyDeregulated Wnt-signaling is a key mechanism driving metastasis in adenocarcinoma of the gastroesophageal junction and stomach (AGE/S). The oncogene <i>S100A4</i> was identified as a Wnt-signaling target gene and is known to promote metastasis. In this project, we illuminate the role of S100A4 for metastases development and disease prognosis of AGE/S. Five gastric cancer cell lines were assessed for S100A4 expression. Two cell lines with endogenous high S100A4 expression were used for functional phenotyping including analysis of proliferation and migration after stable <i>S100A4</i> knock-down. The prognostic value of S100A4 was evaluated by analyzing the S100A4 expression of tissue microarrays with samples of 277 patients with AGE/S. <i>S100A4</i> knock-down induced lower migration in FLO1 and NCI-N87 cells. Treatment with niclosamide in these cells led to partial inhibition of S100A4 and to reduced migration. Patients with high S100A4 expression showed lower 5-year overall and disease-specific survival. In addition, a larger share of patients in the S100A4 high expressing group suffered from metachronous metastasis. This study identifies S100A4 as a negative prognostic marker for patients with AGE/S. The strong correlation between S100A4 expression, metastases development and patient survival might open opportunities to use S100A4 to improve the prognosis of these patients and as a therapeutic target for intervention in this tumor entity.https://www.mdpi.com/2073-4409/11/6/1056gastric canceresophageal cancermetastasisS100A4niclosamide |
| spellingShingle | Christoph Treese Kimberly Hartl Michelle Pötzsch Matthias Dahlmann Moritz von Winterfeld Erika Berg Michael Hummel Lena Timm Beate Rau Wolfgang Walther Severin Daum Dennis Kobelt Ulrike Stein S100A4 Is a Strong Negative Prognostic Marker and Potential Therapeutic Target in Adenocarcinoma of the Stomach and Esophagus Cells gastric cancer esophageal cancer metastasis S100A4 niclosamide |
| title | S100A4 Is a Strong Negative Prognostic Marker and Potential Therapeutic Target in Adenocarcinoma of the Stomach and Esophagus |
| title_full | S100A4 Is a Strong Negative Prognostic Marker and Potential Therapeutic Target in Adenocarcinoma of the Stomach and Esophagus |
| title_fullStr | S100A4 Is a Strong Negative Prognostic Marker and Potential Therapeutic Target in Adenocarcinoma of the Stomach and Esophagus |
| title_full_unstemmed | S100A4 Is a Strong Negative Prognostic Marker and Potential Therapeutic Target in Adenocarcinoma of the Stomach and Esophagus |
| title_short | S100A4 Is a Strong Negative Prognostic Marker and Potential Therapeutic Target in Adenocarcinoma of the Stomach and Esophagus |
| title_sort | s100a4 is a strong negative prognostic marker and potential therapeutic target in adenocarcinoma of the stomach and esophagus |
| topic | gastric cancer esophageal cancer metastasis S100A4 niclosamide |
| url | https://www.mdpi.com/2073-4409/11/6/1056 |
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