Independent Signaling of Hepatoma Derived Growth Factor and Tumor Necrosis Factor-Alpha in Human Gastric Cancer Organoids Infected by <i>Helicobacter pylori</i>
We prepared three-dimensional (3-D) organoids of human stomach cancers and examined the correlation between the tumorigenicity and cytotoxicity of <i>Helicobacter pylori</i> (<i>H. pylori</i>). In addition, the effects of hepatoma-derived growth factor (HDGF) and tumor necros...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6567 |
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| author | Kenly Wuputra Chia-Chen Ku Jia-Bin Pan Chung-Jung Liu Kohsuke Kato Ying-Chu Lin Yi-Chang Liu Chang-Shen Lin Michael Hsiao Ming-Hong Tai Inn-Wen Chong Huang-Ming Hu Chao-Hung Kuo Deng-Chyang Wu Kazunari K. Yokoyama |
| author_facet | Kenly Wuputra Chia-Chen Ku Jia-Bin Pan Chung-Jung Liu Kohsuke Kato Ying-Chu Lin Yi-Chang Liu Chang-Shen Lin Michael Hsiao Ming-Hong Tai Inn-Wen Chong Huang-Ming Hu Chao-Hung Kuo Deng-Chyang Wu Kazunari K. Yokoyama |
| author_sort | Kenly Wuputra |
| collection | DOAJ |
| description | We prepared three-dimensional (3-D) organoids of human stomach cancers and examined the correlation between the tumorigenicity and cytotoxicity of <i>Helicobacter pylori</i> (<i>H. pylori</i>). In addition, the effects of hepatoma-derived growth factor (HDGF) and tumor necrosis factor (TNFα) on the growth and invasion activity of <i>H. pylori</i>-infected gastric cancer organoids were examined. Cytotoxin-associated gene A (CagA)-green fluorescence protein (GFP)-labeled <i>H. pylori</i> was used to trace the infection in gastric organoids. The cytotoxicity of Cag encoded toxins from different species of <i>H. pylori</i> did not affect the proliferation of each <i>H. pylori</i>-infected cancer organoid. To clarify the role of HDGF and TNFα secreted from <i>H. pylori</i>-infected cancer organoids, we prepared recombinant HDGF and TNFα and measured the cytotoxicity and invasion of gastric cancer organoids. HDGF controlled the growth of each organoid in a species-specific manner of <i>H. pylori</i>, but TNFα decreased the cell viability in <i>H. pylori</i>-infected cancer organoids. Furthermore, HDGF controlled the invasion activity of <i>H. pylori</i>-infected cancer organoid in a species-dependent manner. However, TNFα decreased the invasion activities of most organoids. We found different signaling of cytotoxicity and invasion of human gastric organoids in response to HDGF and TNFα during infection by <i>H. pylori</i>. Recombinant HDGF and TNFα inhibited the development and invasion of <i>H. pylori</i>-infected gastric cancer differently. Thus, we propose that HDGF and TNFα are independent signals for development of <i>H. pylori</i>-infected gastric cancer. The signaling of growth factors in 3-D organoid culture systems is different from those in two-dimensional cancer cells. |
| first_indexed | 2024-03-11T05:34:35Z |
| format | Article |
| id | doaj.art-1da16538f0e44597b05f7755e6cfcb24 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:34:35Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1da16538f0e44597b05f7755e6cfcb242023-11-17T16:52:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247656710.3390/ijms24076567Independent Signaling of Hepatoma Derived Growth Factor and Tumor Necrosis Factor-Alpha in Human Gastric Cancer Organoids Infected by <i>Helicobacter pylori</i>Kenly Wuputra0Chia-Chen Ku1Jia-Bin Pan2Chung-Jung Liu3Kohsuke Kato4Ying-Chu Lin5Yi-Chang Liu6Chang-Shen Lin7Michael Hsiao8Ming-Hong Tai9Inn-Wen Chong10Huang-Ming Hu11Chao-Hung Kuo12Deng-Chyang Wu13Kazunari K. Yokoyama14Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanRegenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Infection Biology, Graduate School of Comprehensive Human Sciences, The University of Tsukuba, Tsukuba 305-8577, JapanSchool of Dentistry, Kaohsiung Medical University, Kaohsiung 80756, TaiwanCell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung 80756, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGenome Research Center, Academia Sinica, Nangan, Taipei 11529, TaiwanInstitute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 80424, TaiwanDivision of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, TaiwanDepartment of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, TaiwanDivision of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, TaiwanRegenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanWe prepared three-dimensional (3-D) organoids of human stomach cancers and examined the correlation between the tumorigenicity and cytotoxicity of <i>Helicobacter pylori</i> (<i>H. pylori</i>). In addition, the effects of hepatoma-derived growth factor (HDGF) and tumor necrosis factor (TNFα) on the growth and invasion activity of <i>H. pylori</i>-infected gastric cancer organoids were examined. Cytotoxin-associated gene A (CagA)-green fluorescence protein (GFP)-labeled <i>H. pylori</i> was used to trace the infection in gastric organoids. The cytotoxicity of Cag encoded toxins from different species of <i>H. pylori</i> did not affect the proliferation of each <i>H. pylori</i>-infected cancer organoid. To clarify the role of HDGF and TNFα secreted from <i>H. pylori</i>-infected cancer organoids, we prepared recombinant HDGF and TNFα and measured the cytotoxicity and invasion of gastric cancer organoids. HDGF controlled the growth of each organoid in a species-specific manner of <i>H. pylori</i>, but TNFα decreased the cell viability in <i>H. pylori</i>-infected cancer organoids. Furthermore, HDGF controlled the invasion activity of <i>H. pylori</i>-infected cancer organoid in a species-dependent manner. However, TNFα decreased the invasion activities of most organoids. We found different signaling of cytotoxicity and invasion of human gastric organoids in response to HDGF and TNFα during infection by <i>H. pylori</i>. Recombinant HDGF and TNFα inhibited the development and invasion of <i>H. pylori</i>-infected gastric cancer differently. Thus, we propose that HDGF and TNFα are independent signals for development of <i>H. pylori</i>-infected gastric cancer. The signaling of growth factors in 3-D organoid culture systems is different from those in two-dimensional cancer cells.https://www.mdpi.com/1422-0067/24/7/6567<i>Helicobacter pylori</i>hepatoma-derived growth factorinvasion activitygastric cancer organoidstumor necrosis factor α |
| spellingShingle | Kenly Wuputra Chia-Chen Ku Jia-Bin Pan Chung-Jung Liu Kohsuke Kato Ying-Chu Lin Yi-Chang Liu Chang-Shen Lin Michael Hsiao Ming-Hong Tai Inn-Wen Chong Huang-Ming Hu Chao-Hung Kuo Deng-Chyang Wu Kazunari K. Yokoyama Independent Signaling of Hepatoma Derived Growth Factor and Tumor Necrosis Factor-Alpha in Human Gastric Cancer Organoids Infected by <i>Helicobacter pylori</i> International Journal of Molecular Sciences <i>Helicobacter pylori</i> hepatoma-derived growth factor invasion activity gastric cancer organoids tumor necrosis factor α |
| title | Independent Signaling of Hepatoma Derived Growth Factor and Tumor Necrosis Factor-Alpha in Human Gastric Cancer Organoids Infected by <i>Helicobacter pylori</i> |
| title_full | Independent Signaling of Hepatoma Derived Growth Factor and Tumor Necrosis Factor-Alpha in Human Gastric Cancer Organoids Infected by <i>Helicobacter pylori</i> |
| title_fullStr | Independent Signaling of Hepatoma Derived Growth Factor and Tumor Necrosis Factor-Alpha in Human Gastric Cancer Organoids Infected by <i>Helicobacter pylori</i> |
| title_full_unstemmed | Independent Signaling of Hepatoma Derived Growth Factor and Tumor Necrosis Factor-Alpha in Human Gastric Cancer Organoids Infected by <i>Helicobacter pylori</i> |
| title_short | Independent Signaling of Hepatoma Derived Growth Factor and Tumor Necrosis Factor-Alpha in Human Gastric Cancer Organoids Infected by <i>Helicobacter pylori</i> |
| title_sort | independent signaling of hepatoma derived growth factor and tumor necrosis factor alpha in human gastric cancer organoids infected by i helicobacter pylori i |
| topic | <i>Helicobacter pylori</i> hepatoma-derived growth factor invasion activity gastric cancer organoids tumor necrosis factor α |
| url | https://www.mdpi.com/1422-0067/24/7/6567 |
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