S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis
S100A4 plays important roles in tumor development and metastasis, but its role in regulating inflammation and colitis-associated tumorigenesis has not been well characterized. Here, we report that S100A4 expression was increased in azoxymethane (AOM) and dextran sulfate sodium (DSS) induced colorect...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-08-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2018.1461301 |
| _version_ | 1811204302443642880 |
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| author | Jinhua Zhang Shasha Hou Jianchun Gu Tian Tian Qi Yuan Junying Jia Zhihai Qin Zhinan Chen |
| author_facet | Jinhua Zhang Shasha Hou Jianchun Gu Tian Tian Qi Yuan Junying Jia Zhihai Qin Zhinan Chen |
| author_sort | Jinhua Zhang |
| collection | DOAJ |
| description | S100A4 plays important roles in tumor development and metastasis, but its role in regulating inflammation and colitis-associated tumorigenesis has not been well characterized. Here, we report that S100A4 expression was increased in azoxymethane (AOM) and dextran sulfate sodium (DSS) induced colorectal cancer (CRC) in mice. After AOM/DSS treatment, both S100A4-TK mice with the selective depletion of S100A4-expressing cells and S100A4-deficient (S100A4−/−) mice developed fewer and smaller tumors than wild-type (WT) control littermates. Furthermore, S100A4−/− mice were resistant to DSS-induced colitis, reduced infiltration of macrophages, and the diminished production of proinflammatory cytokines. Further studies revealed that reduced colon inflammation and colorectal tumor development in S100A4−/− mice were partly due to the dampening of nuclear factor (NF)-κB activation in macrophages. Furthermore, the administration of a neutralizing S100A4 antibody to WT mice significantly decreased AOM/DSS-induced colon inflammation and tumorigenesis. These results indicate that S100A4 amplifies an inflammatory microenvironment that promotes colon tumorigenesis and provides a promising therapeutic strategy for treatment of inflammatory bowel disease and prevention of colitis-associated colorectal carcinogenesis. |
| first_indexed | 2024-04-12T03:12:06Z |
| format | Article |
| id | doaj.art-4f4b341be30843939c5296a1df30e5be |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-04-12T03:12:06Z |
| publishDate | 2018-08-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-4f4b341be30843939c5296a1df30e5be2022-12-22T03:50:20ZengTaylor & Francis GroupOncoImmunology2162-402X2018-08-017810.1080/2162402X.2018.14613011461301S100A4 promotes colon inflammation and colitis-associated colon tumorigenesisJinhua Zhang0Shasha Hou1Jianchun Gu2Tian Tian3Qi Yuan4Junying Jia5Zhihai Qin6Zhinan Chen7College of Life Science and Bioengineering, Beijing Jiaotong UniversityCollege of Life Science and Bioengineering, Beijing Jiaotong UniversityXinhua Hospital Affiliated to Shanghai Jiaotong University School of MedicineCollege of Life Science and Bioengineering, Beijing Jiaotong UniversityCollege of Life Science and Bioengineering, Beijing Jiaotong UniversityCore Facility Center, Institute of Biophysics, Chinese Academy of SciencesChinese Academy of SciencesCollege of Life Science and Bioengineering, Beijing Jiaotong UniversityS100A4 plays important roles in tumor development and metastasis, but its role in regulating inflammation and colitis-associated tumorigenesis has not been well characterized. Here, we report that S100A4 expression was increased in azoxymethane (AOM) and dextran sulfate sodium (DSS) induced colorectal cancer (CRC) in mice. After AOM/DSS treatment, both S100A4-TK mice with the selective depletion of S100A4-expressing cells and S100A4-deficient (S100A4−/−) mice developed fewer and smaller tumors than wild-type (WT) control littermates. Furthermore, S100A4−/− mice were resistant to DSS-induced colitis, reduced infiltration of macrophages, and the diminished production of proinflammatory cytokines. Further studies revealed that reduced colon inflammation and colorectal tumor development in S100A4−/− mice were partly due to the dampening of nuclear factor (NF)-κB activation in macrophages. Furthermore, the administration of a neutralizing S100A4 antibody to WT mice significantly decreased AOM/DSS-induced colon inflammation and tumorigenesis. These results indicate that S100A4 amplifies an inflammatory microenvironment that promotes colon tumorigenesis and provides a promising therapeutic strategy for treatment of inflammatory bowel disease and prevention of colitis-associated colorectal carcinogenesis.http://dx.doi.org/10.1080/2162402X.2018.1461301s100a4colitiscolorectal cancerinflammationtumorigenesis |
| spellingShingle | Jinhua Zhang Shasha Hou Jianchun Gu Tian Tian Qi Yuan Junying Jia Zhihai Qin Zhinan Chen S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis OncoImmunology s100a4 colitis colorectal cancer inflammation tumorigenesis |
| title | S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis |
| title_full | S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis |
| title_fullStr | S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis |
| title_full_unstemmed | S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis |
| title_short | S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis |
| title_sort | s100a4 promotes colon inflammation and colitis associated colon tumorigenesis |
| topic | s100a4 colitis colorectal cancer inflammation tumorigenesis |
| url | http://dx.doi.org/10.1080/2162402X.2018.1461301 |
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