Claudin-3 inhibits tumor-induced lymphangiogenesis via regulating the PI3K signaling pathway in lymphatic endothelial cells
Abstract Claudin-3 is a tight junction protein that has often been associated with the progression and metastasis of various tumors. Here, the role of claudin-3 in tumor-induced lymphangiogenesis is investigated. We found an increased lymphangiogenesis in the B16F10 tumor in claudin-3 knockout mice,...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-22156-6 |
| _version_ | 1811336572441722880 |
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| author | Ningjing Lei Yanru Cheng Jiajia Wan Rosel Blasig Anqi Li Yueyue Bai Reiner F. Haseloff Ingolf E. Blasig Linyu Zhu Zhihai Qin |
| author_facet | Ningjing Lei Yanru Cheng Jiajia Wan Rosel Blasig Anqi Li Yueyue Bai Reiner F. Haseloff Ingolf E. Blasig Linyu Zhu Zhihai Qin |
| author_sort | Ningjing Lei |
| collection | DOAJ |
| description | Abstract Claudin-3 is a tight junction protein that has often been associated with the progression and metastasis of various tumors. Here, the role of claudin-3 in tumor-induced lymphangiogenesis is investigated. We found an increased lymphangiogenesis in the B16F10 tumor in claudin-3 knockout mice, accompanied by augmented melanoma cell metastasis into sentinel lymph nodes. In vitro, the overexpression of claudin-3 on lymphatic endothelial cells inhibited tube formation by suppressing cell migration, resulting in restricted lymphangiogenesis. Further experiments showed that claudin-3 inhibited lymphatic endothelial cell migration by regulating the PI3K signaling pathway. Interestingly, the expression of claudin-3 in lymphatic endothelial cells is down-regulated by vascular endothelial growth factor C that is often present in the tumor microenvironment. This study indicates that claudin-3 plays an important role as a signaling molecule in lymphatic endothelial cell activity associated with tumor lymphangiogenesis, which may further contribute to melanoma metastasis. |
| first_indexed | 2024-04-13T17:41:23Z |
| format | Article |
| id | doaj.art-59ed644337784e4193efb81bc0cb0487 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T17:41:23Z |
| publishDate | 2022-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-59ed644337784e4193efb81bc0cb04872022-12-22T02:37:10ZengNature PortfolioScientific Reports2045-23222022-10-0112111310.1038/s41598-022-22156-6Claudin-3 inhibits tumor-induced lymphangiogenesis via regulating the PI3K signaling pathway in lymphatic endothelial cellsNingjing Lei0Yanru Cheng1Jiajia Wan2Rosel Blasig3Anqi Li4Yueyue Bai5Reiner F. Haseloff6Ingolf E. Blasig7Linyu Zhu8Zhihai Qin9Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityMedical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityMedical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityLeibniz-Forschungsinstitut Für Molekulare Pharmakologie (FMP)Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityMedical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityLeibniz-Forschungsinstitut Für Molekulare Pharmakologie (FMP)Leibniz-Forschungsinstitut Für Molekulare Pharmakologie (FMP)Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityMedical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityAbstract Claudin-3 is a tight junction protein that has often been associated with the progression and metastasis of various tumors. Here, the role of claudin-3 in tumor-induced lymphangiogenesis is investigated. We found an increased lymphangiogenesis in the B16F10 tumor in claudin-3 knockout mice, accompanied by augmented melanoma cell metastasis into sentinel lymph nodes. In vitro, the overexpression of claudin-3 on lymphatic endothelial cells inhibited tube formation by suppressing cell migration, resulting in restricted lymphangiogenesis. Further experiments showed that claudin-3 inhibited lymphatic endothelial cell migration by regulating the PI3K signaling pathway. Interestingly, the expression of claudin-3 in lymphatic endothelial cells is down-regulated by vascular endothelial growth factor C that is often present in the tumor microenvironment. This study indicates that claudin-3 plays an important role as a signaling molecule in lymphatic endothelial cell activity associated with tumor lymphangiogenesis, which may further contribute to melanoma metastasis.https://doi.org/10.1038/s41598-022-22156-6 |
| spellingShingle | Ningjing Lei Yanru Cheng Jiajia Wan Rosel Blasig Anqi Li Yueyue Bai Reiner F. Haseloff Ingolf E. Blasig Linyu Zhu Zhihai Qin Claudin-3 inhibits tumor-induced lymphangiogenesis via regulating the PI3K signaling pathway in lymphatic endothelial cells Scientific Reports |
| title | Claudin-3 inhibits tumor-induced lymphangiogenesis via regulating the PI3K signaling pathway in lymphatic endothelial cells |
| title_full | Claudin-3 inhibits tumor-induced lymphangiogenesis via regulating the PI3K signaling pathway in lymphatic endothelial cells |
| title_fullStr | Claudin-3 inhibits tumor-induced lymphangiogenesis via regulating the PI3K signaling pathway in lymphatic endothelial cells |
| title_full_unstemmed | Claudin-3 inhibits tumor-induced lymphangiogenesis via regulating the PI3K signaling pathway in lymphatic endothelial cells |
| title_short | Claudin-3 inhibits tumor-induced lymphangiogenesis via regulating the PI3K signaling pathway in lymphatic endothelial cells |
| title_sort | claudin 3 inhibits tumor induced lymphangiogenesis via regulating the pi3k signaling pathway in lymphatic endothelial cells |
| url | https://doi.org/10.1038/s41598-022-22156-6 |
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