Targeting Tumor Endothelial Cells by EGCG Using Specific Liposome Delivery System Inhibits Vascular Inflammation and Thrombosis
ABSTRACT Background Inflammation is one of the hallmarks of cancer and is associated with tumor growth. Tumor endothelial cells (TECs) demonstrate inflamed phenotypes. Endothelial inflammation initiates thrombus formation, which is the second cause of cancer‐related deaths. Epigallocatechin‐3‐O‐gall...
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| Format: | Article |
| Language: | English |
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Wiley
2024-12-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70462 |
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| author | Zi Jia Nako Maishi Hideki Takekawa Aya Yanagawa Matsuda Taisei Nakade Takashi Nakamura Hideyoshi Harashima Yasuhiro Hida Kyoko Hida |
| author_facet | Zi Jia Nako Maishi Hideki Takekawa Aya Yanagawa Matsuda Taisei Nakade Takashi Nakamura Hideyoshi Harashima Yasuhiro Hida Kyoko Hida |
| author_sort | Zi Jia |
| collection | DOAJ |
| description | ABSTRACT Background Inflammation is one of the hallmarks of cancer and is associated with tumor growth. Tumor endothelial cells (TECs) demonstrate inflamed phenotypes. Endothelial inflammation initiates thrombus formation, which is the second cause of cancer‐related deaths. Epigallocatechin‐3‐O‐gallate (EGCG), a natural compound in green tea, has demonstrated an anti‐inflammatory effect. However, the tumor progression inhibition effect of EGCG by targeting TEC inflammation remains unclear. This study addresses the anti‐tumor effect of EGCG, especially its anti‐inflammatory role in TECs. Methods In vitro, the effect of EGCG on TECs were studied using real‐time quantitative PCR and immunofluoresence to analyza gene and protein expression. In vivo, a cyclic RGD liposome delivery system (MEND) was employed to efficiently deliver EGCG to TECs in tumor‐bearing mice. Results In vitro, EGCG significantly reduces inflammatory cytokine expression, including tumor necrosis factor‐α, interleukin‐6, IL‐8, and IL‐1β through NF‐κB signaling inhibition. Additionally, von Willebrand factor reduction in TECs, which is involved in platelet adhesion and thrombosis formation, was analyzed. Our results revealed that EGCG‐MEND significantly inhibited TEC inflammation and thrombus formation in tumors. Additionally, EGCG‐MEND improved tumor immunity by reducing programmed death‐ligand 1 expression and promoting high endothelial venule formation by recruiting CD8+ T cells. Conclusion Our results indicate the anti‐tumor potential of EGCG‐MEND in normalizing the inflammatory immune microenvironment and inhibiting thrombosis by targeting TEC. |
| format | Article |
| id | doaj-art-57b0ce65e24c4244a211bd8a7afeaf53 |
| institution | OA Journals |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-57b0ce65e24c4244a211bd8a7afeaf532025-08-20T01:58:46ZengWileyCancer Medicine2045-76342024-12-011323n/an/a10.1002/cam4.70462Targeting Tumor Endothelial Cells by EGCG Using Specific Liposome Delivery System Inhibits Vascular Inflammation and ThrombosisZi Jia0Nako Maishi1Hideki Takekawa2Aya Yanagawa Matsuda3Taisei Nakade4Takashi Nakamura5Hideyoshi Harashima6Yasuhiro Hida7Kyoko Hida8Vascular Biology and Molecular Pathology Hokkaido University Graduate School of Dental Medicine Sapporo JapanVascular Biology and Molecular Pathology Hokkaido University Graduate School of Dental Medicine Sapporo JapanVascular Biology and Molecular Pathology Hokkaido University Graduate School of Dental Medicine Sapporo JapanVascular Biology and Molecular Pathology Hokkaido University Graduate School of Dental Medicine Sapporo JapanFaculty of Pharmaceutical Sciences Hokkaido University Sapporo JapanFaculty of Pharmaceutical Sciences Hokkaido University Sapporo JapanFaculty of Pharmaceutical Sciences Hokkaido University Sapporo JapanAdvanced Robotic and Endoscopic Surgery School of Medicine, Fujita Health University Toyoake JapanVascular Biology and Molecular Pathology Hokkaido University Graduate School of Dental Medicine Sapporo JapanABSTRACT Background Inflammation is one of the hallmarks of cancer and is associated with tumor growth. Tumor endothelial cells (TECs) demonstrate inflamed phenotypes. Endothelial inflammation initiates thrombus formation, which is the second cause of cancer‐related deaths. Epigallocatechin‐3‐O‐gallate (EGCG), a natural compound in green tea, has demonstrated an anti‐inflammatory effect. However, the tumor progression inhibition effect of EGCG by targeting TEC inflammation remains unclear. This study addresses the anti‐tumor effect of EGCG, especially its anti‐inflammatory role in TECs. Methods In vitro, the effect of EGCG on TECs were studied using real‐time quantitative PCR and immunofluoresence to analyza gene and protein expression. In vivo, a cyclic RGD liposome delivery system (MEND) was employed to efficiently deliver EGCG to TECs in tumor‐bearing mice. Results In vitro, EGCG significantly reduces inflammatory cytokine expression, including tumor necrosis factor‐α, interleukin‐6, IL‐8, and IL‐1β through NF‐κB signaling inhibition. Additionally, von Willebrand factor reduction in TECs, which is involved in platelet adhesion and thrombosis formation, was analyzed. Our results revealed that EGCG‐MEND significantly inhibited TEC inflammation and thrombus formation in tumors. Additionally, EGCG‐MEND improved tumor immunity by reducing programmed death‐ligand 1 expression and promoting high endothelial venule formation by recruiting CD8+ T cells. Conclusion Our results indicate the anti‐tumor potential of EGCG‐MEND in normalizing the inflammatory immune microenvironment and inhibiting thrombosis by targeting TEC.https://doi.org/10.1002/cam4.70462EGCGROStumor endothelial celltumor inflammationtumor thrombosis |
| spellingShingle | Zi Jia Nako Maishi Hideki Takekawa Aya Yanagawa Matsuda Taisei Nakade Takashi Nakamura Hideyoshi Harashima Yasuhiro Hida Kyoko Hida Targeting Tumor Endothelial Cells by EGCG Using Specific Liposome Delivery System Inhibits Vascular Inflammation and Thrombosis Cancer Medicine EGCG ROS tumor endothelial cell tumor inflammation tumor thrombosis |
| title | Targeting Tumor Endothelial Cells by EGCG Using Specific Liposome Delivery System Inhibits Vascular Inflammation and Thrombosis |
| title_full | Targeting Tumor Endothelial Cells by EGCG Using Specific Liposome Delivery System Inhibits Vascular Inflammation and Thrombosis |
| title_fullStr | Targeting Tumor Endothelial Cells by EGCG Using Specific Liposome Delivery System Inhibits Vascular Inflammation and Thrombosis |
| title_full_unstemmed | Targeting Tumor Endothelial Cells by EGCG Using Specific Liposome Delivery System Inhibits Vascular Inflammation and Thrombosis |
| title_short | Targeting Tumor Endothelial Cells by EGCG Using Specific Liposome Delivery System Inhibits Vascular Inflammation and Thrombosis |
| title_sort | targeting tumor endothelial cells by egcg using specific liposome delivery system inhibits vascular inflammation and thrombosis |
| topic | EGCG ROS tumor endothelial cell tumor inflammation tumor thrombosis |
| url | https://doi.org/10.1002/cam4.70462 |
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