IL‑10 secreted by cancer‑associated macrophages regulates proliferation and invasion in gastric cancer cells via c‑Met/STAT3 signaling
Gastric cancer is one of the most common types of human cancer, and it is additionally one of the leading causes of cancer‑associated mortality worldwide. Previous studies have suggested that interleukin (IL)‑10 may contribute to the pathogenesis of gastric cancer. However, the underlying mechanisms...
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| Veröffentlicht in: | Oncology reports 2019-08, Vol.42 (2), p.595-604 |
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| creator | Chen, Ling Shi, Yuntao Zhu, Xiaojuan Guo, Weiwei Zhang, Mingjiong Che, Ying Tang, Lijuan Yang, Xiaozhong You, Qiang Liu, Zheng |
| description | Gastric cancer is one of the most common types of human cancer, and it is additionally one of the leading causes of cancer‑associated mortality worldwide. Previous studies have suggested that interleukin (IL)‑10 may contribute to the pathogenesis of gastric cancer. However, the underlying mechanisms remain unclear. In the present study, it was observed that the expression of IL‑10 was significantly upregulated in gastric tumor tissues and serum samples of patients with gastric cancer. Furthermore, IL‑10 was increased in the cell culture supernatant of cancer‑associated macrophages (CAMs). Treatment with cell culture supernatant from CAMs induced a significant increase in proliferation and migration, while it suppressed apoptosis, in MGC‑803 and BGC‑823 gastric cancer cells. Notably, application of an inhibitory IL‑10 antibody partially blocked the cell culture supernatant of CAM‑induced oncogenic effects. RNA‑sequencing analysis was then performed to identify the differentially expressed genes in MGC‑803 cells treated with IL‑10. Based on the sequencing results and in vitro analysis, it was demonstrated that IL‑10‑induced carcinogenic behaviors in MGC‑803 cells were potentially mediated by activation of the c‑Met/STAT3 signaling pathway. In conclusion, the present results demonstrated that IL‑10 secreted by CAMs may be involved in the pathogenesis of gastric cancer, suggesting that IL‑10 may serve as a potential therapeutic target for the treatment of gastric cancer. |
| doi_str_mv | 10.3892/or.2019.7206 |
| format | Article |
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Previous studies have suggested that interleukin (IL)‑10 may contribute to the pathogenesis of gastric cancer. However, the underlying mechanisms remain unclear. In the present study, it was observed that the expression of IL‑10 was significantly upregulated in gastric tumor tissues and serum samples of patients with gastric cancer. Furthermore, IL‑10 was increased in the cell culture supernatant of cancer‑associated macrophages (CAMs). Treatment with cell culture supernatant from CAMs induced a significant increase in proliferation and migration, while it suppressed apoptosis, in MGC‑803 and BGC‑823 gastric cancer cells. Notably, application of an inhibitory IL‑10 antibody partially blocked the cell culture supernatant of CAM‑induced oncogenic effects. RNA‑sequencing analysis was then performed to identify the differentially expressed genes in MGC‑803 cells treated with IL‑10. Based on the sequencing results and in vitro analysis, it was demonstrated that IL‑10‑induced carcinogenic behaviors in MGC‑803 cells were potentially mediated by activation of the c‑Met/STAT3 signaling pathway. In conclusion, the present results demonstrated that IL‑10 secreted by CAMs may be involved in the pathogenesis of gastric cancer, suggesting that IL‑10 may serve as a potential therapeutic target for the treatment of gastric cancer.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or.2019.7206</identifier><identifier>PMID: 31233202</identifier><language>eng</language><publisher>Greece: Spandidos Publications</publisher><subject>Aged ; Antibodies ; Apoptosis ; Biomarkers, Tumor - metabolism ; Cancer ; Cancer cells ; Cancer therapies ; Case-Control Studies ; Cell culture ; Cell growth ; Cell Proliferation ; Computer aided manufacturing ; Cytokines ; Development and progression ; Female ; Gastric cancer ; Gastrointestinal diseases ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genes ; Health aspects ; Humans ; Interleukin-10 - metabolism ; Interleukins ; Kinases ; Macrophages ; Macrophages - metabolism ; Macrophages - pathology ; Male ; Medical prognosis ; Metastasis ; Middle Aged ; Mortality ; Pathogenesis ; Prognosis ; Proto-Oncogene Proteins c-met - metabolism ; RNA ; Roles ; Scientific equipment industry ; STAT3 Transcription Factor - metabolism ; Stomach cancer ; Stomach Neoplasms - metabolism ; Stomach Neoplasms - pathology ; Studies ; Tumor Cells, Cultured ; Tumors ; United States</subject><ispartof>Oncology reports, 2019-08, Vol.42 (2), p.595-604</ispartof><rights>COPYRIGHT 2019 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2019</rights><rights>Copyright: © Chen et al. 2019</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c576t-bfe55538f36ac029568301cc8c43e6a927452c5c9520c63d9ad58c92d33703173</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31233202$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Ling</creatorcontrib><creatorcontrib>Shi, Yuntao</creatorcontrib><creatorcontrib>Zhu, Xiaojuan</creatorcontrib><creatorcontrib>Guo, Weiwei</creatorcontrib><creatorcontrib>Zhang, Mingjiong</creatorcontrib><creatorcontrib>Che, Ying</creatorcontrib><creatorcontrib>Tang, Lijuan</creatorcontrib><creatorcontrib>Yang, Xiaozhong</creatorcontrib><creatorcontrib>You, Qiang</creatorcontrib><creatorcontrib>Liu, Zheng</creatorcontrib><title>IL‑10 secreted by cancer‑associated macrophages regulates proliferation and invasion in gastric cancer cells via c‑Met/STAT3 signaling</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>Gastric cancer is one of the most common types of human cancer, and it is additionally one of the leading causes of cancer‑associated mortality worldwide. Previous studies have suggested that interleukin (IL)‑10 may contribute to the pathogenesis of gastric cancer. However, the underlying mechanisms remain unclear. In the present study, it was observed that the expression of IL‑10 was significantly upregulated in gastric tumor tissues and serum samples of patients with gastric cancer. Furthermore, IL‑10 was increased in the cell culture supernatant of cancer‑associated macrophages (CAMs). Treatment with cell culture supernatant from CAMs induced a significant increase in proliferation and migration, while it suppressed apoptosis, in MGC‑803 and BGC‑823 gastric cancer cells. Notably, application of an inhibitory IL‑10 antibody partially blocked the cell culture supernatant of CAM‑induced oncogenic effects. RNA‑sequencing analysis was then performed to identify the differentially expressed genes in MGC‑803 cells treated with IL‑10. Based on the sequencing results and in vitro analysis, it was demonstrated that IL‑10‑induced carcinogenic behaviors in MGC‑803 cells were potentially mediated by activation of the c‑Met/STAT3 signaling pathway. In conclusion, the present results demonstrated that IL‑10 secreted by CAMs may be involved in the pathogenesis of gastric cancer, suggesting that IL‑10 may serve as a potential therapeutic target for the treatment of gastric cancer.</description><subject>Aged</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Cancer</subject><subject>Cancer cells</subject><subject>Cancer therapies</subject><subject>Case-Control Studies</subject><subject>Cell culture</subject><subject>Cell growth</subject><subject>Cell Proliferation</subject><subject>Computer aided manufacturing</subject><subject>Cytokines</subject><subject>Development and progression</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Gastrointestinal diseases</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Interleukin-10 - metabolism</subject><subject>Interleukins</subject><subject>Kinases</subject><subject>Macrophages</subject><subject>Macrophages - metabolism</subject><subject>Macrophages - pathology</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Pathogenesis</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins c-met - metabolism</subject><subject>RNA</subject><subject>Roles</subject><subject>Scientific equipment industry</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>Stomach cancer</subject><subject>Stomach Neoplasms - metabolism</subject><subject>Stomach Neoplasms - pathology</subject><subject>Studies</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><subject>United States</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptkk9rFDEYxgdRbK3ePEtA6KmzzZ9JZnIRlmK1sOLBFbyF7DuZ2ZRMsiYzC735Abz4Ff0kZuhauyA5JHnyex_yJk9RvCZ4wRpJL0NcUEzkoqZYPClOSS1JSStGnuY1pqRkjH87KV6kdIsxrbGQz4sTRihjFNPT4ufN6vePXwSjZCCa0bRoc4dAezAx6zqlAFbP8qAhht1W9yahaPrJZTWhXQzOdibq0QaPtG-R9Xud5o31qNdpjBYOfgiMcwntrUaQvT-Z8fLLerlmKNnea2d9_7J41mmXzKvDfFZ8vX6_vvpYrj5_uLlarkrgtRjLTWc456zpmNCAqeSiYZgANFAxI7SkdcUpcJCcYhCslbrlDUjaMlZjRmp2Vry7991Nm8G0YPwYtVO7aAcd71TQVh2feLtVfdgrIQjGbDZ4ezCI4ftk0qhuwxRzE0lRmu8mSS2qf1SvnVHWdyGbwWATqCWXVcMoqUmmFv-h8mjNYCF409msHxWcPyrYGu3GbQpumr8gHYMX92D-uZSi6R46JFjN2VEhqjk7as5Oxt88fpUH-G9Y2B8RecFw</recordid><startdate>20190801</startdate><enddate>20190801</enddate><creator>Chen, Ling</creator><creator>Shi, Yuntao</creator><creator>Zhu, Xiaojuan</creator><creator>Guo, Weiwei</creator><creator>Zhang, Mingjiong</creator><creator>Che, Ying</creator><creator>Tang, Lijuan</creator><creator>Yang, Xiaozhong</creator><creator>You, Qiang</creator><creator>Liu, Zheng</creator><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><general>D.A. 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Previous studies have suggested that interleukin (IL)‑10 may contribute to the pathogenesis of gastric cancer. However, the underlying mechanisms remain unclear. In the present study, it was observed that the expression of IL‑10 was significantly upregulated in gastric tumor tissues and serum samples of patients with gastric cancer. Furthermore, IL‑10 was increased in the cell culture supernatant of cancer‑associated macrophages (CAMs). Treatment with cell culture supernatant from CAMs induced a significant increase in proliferation and migration, while it suppressed apoptosis, in MGC‑803 and BGC‑823 gastric cancer cells. Notably, application of an inhibitory IL‑10 antibody partially blocked the cell culture supernatant of CAM‑induced oncogenic effects. RNA‑sequencing analysis was then performed to identify the differentially expressed genes in MGC‑803 cells treated with IL‑10. Based on the sequencing results and in vitro analysis, it was demonstrated that IL‑10‑induced carcinogenic behaviors in MGC‑803 cells were potentially mediated by activation of the c‑Met/STAT3 signaling pathway. In conclusion, the present results demonstrated that IL‑10 secreted by CAMs may be involved in the pathogenesis of gastric cancer, suggesting that IL‑10 may serve as a potential therapeutic target for the treatment of gastric cancer.</abstract><cop>Greece</cop><pub>Spandidos Publications</pub><pmid>31233202</pmid><doi>10.3892/or.2019.7206</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Antibodies Apoptosis Biomarkers, Tumor - metabolism Cancer Cancer cells Cancer therapies Case-Control Studies Cell culture Cell growth Cell Proliferation Computer aided manufacturing Cytokines Development and progression Female Gastric cancer Gastrointestinal diseases Gene expression Gene Expression Regulation, Neoplastic Genes Health aspects Humans Interleukin-10 - metabolism Interleukins Kinases Macrophages Macrophages - metabolism Macrophages - pathology Male Medical prognosis Metastasis Middle Aged Mortality Pathogenesis Prognosis Proto-Oncogene Proteins c-met - metabolism RNA Roles Scientific equipment industry STAT3 Transcription Factor - metabolism Stomach cancer Stomach Neoplasms - metabolism Stomach Neoplasms - pathology Studies Tumor Cells, Cultured Tumors United States |
| title | IL‑10 secreted by cancer‑associated macrophages regulates proliferation and invasion in gastric cancer cells via c‑Met/STAT3 signaling |
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