Concurrent Blockade of Endothelial EGFR and VEGF Signaling on Malignant Associated Pleural Fluid Induced Angiogenesis: From Clinic to Bench
Malignant-associated pleural fluid (MAPF) represented an unsolved problem in advanced lung cancer. Our previous work characterized increased pleural angiogenesis in lung adenocarcinoma and the propensity of MAPF on endothelial angiogenesis. This study investigated the combined efficacy of the tyrosi...
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MDPI AG
2021-09-01
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| Online Access: | https://www.mdpi.com/2227-9059/9/10/1327 |
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| author | Wei-Teing Chen Yu-Huei Lin Chih-Ying Changchien Ying Chen Hsin-Han Chang Wen-Chiuan Tsai Hao-Chung Tsai Chieh-Yung Wang Ming-Sheng Shen Li-Ting Cheng Chen-Liang Tsai |
| author_facet | Wei-Teing Chen Yu-Huei Lin Chih-Ying Changchien Ying Chen Hsin-Han Chang Wen-Chiuan Tsai Hao-Chung Tsai Chieh-Yung Wang Ming-Sheng Shen Li-Ting Cheng Chen-Liang Tsai |
| author_sort | Wei-Teing Chen |
| collection | DOAJ |
| description | Malignant-associated pleural fluid (MAPF) represented an unsolved problem in advanced lung cancer. Our previous work characterized increased pleural angiogenesis in lung adenocarcinoma and the propensity of MAPF on endothelial angiogenesis. This study investigated the combined efficacy of the tyrosine kinase inhibitor (gefitinib) and bevacizumab in opposing MAPF-induced angiogenesis. In lung adenocarcinoma patients with malignant pleural effusion (MPE), Kaplan–Meier analysis revealed the benefit of cotreatment with target therapy and bevacizumab. Increased EGFR expression was observed in the pleural microvessels of patients with lung adenocarcinoma both with and without mutations in EGFR. MAPF was obtained from lung adenocarcinoma patients both wild-type and mutant EGFRs. Total and phosphorylated EGFR were upregulated in HUVEC cultured with MAPF. Treatment with gefitinib as an EGFR inhibitor suppressed MAPF-induced endothelial migration and partially attenuated endothelial proliferation in both wild-type and mutant EGFR lung adenocarcinoma. Cotreatment with gefitinib and bevacizumab produced better inhibition of MAPF-induced endothelial angiogenesis than gefitinib alone in the mutant EGFR subgroup. Protein analysis of MAPF-derived exosomes revealed abundant EGFR and p-EGFR components that implied possible transfer to endothelial cells. Concluding Kaplan–Meier analysis and in vitro studies, the results indicated that the addition of bevacizumab on gefitinib treatment could suppress MAPF-induced angiogenesis in lung adenocarcinoma patients. |
| first_indexed | 2024-03-10T06:43:49Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T06:43:49Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-d7a4d0e19f774a0bbbd90117b07a80b52023-11-22T17:30:09ZengMDPI AGBiomedicines2227-90592021-09-01910132710.3390/biomedicines9101327Concurrent Blockade of Endothelial EGFR and VEGF Signaling on Malignant Associated Pleural Fluid Induced Angiogenesis: From Clinic to BenchWei-Teing Chen0Yu-Huei Lin1Chih-Ying Changchien2Ying Chen3Hsin-Han Chang4Wen-Chiuan Tsai5Hao-Chung Tsai6Chieh-Yung Wang7Ming-Sheng Shen8Li-Ting Cheng9Chen-Liang Tsai10Division of Chest Medicine, Department of Medicine, Cheng-Hsin General Hospital, Taipei 112, TaiwanPost-Baccalaureate Program in Nursing, College of Nursing, Taipei Medical University, Taipei 110, TaiwanDepartment of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDepartment of Biology and Anatomy, National Defense Medical Center, Taipei 114, TaiwanDepartment of Biology and Anatomy, National Defense Medical Center, Taipei 114, TaiwanDepartment of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDivision of Chest Medicine, Department of Internal Medicine, Tri-Service General Hospital Songshan Branch, Taipei 105, TaiwanDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDepartment of Internal Medicine, Taichung Armed Force General Hospital, Taichung 411, TaiwanDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanMalignant-associated pleural fluid (MAPF) represented an unsolved problem in advanced lung cancer. Our previous work characterized increased pleural angiogenesis in lung adenocarcinoma and the propensity of MAPF on endothelial angiogenesis. This study investigated the combined efficacy of the tyrosine kinase inhibitor (gefitinib) and bevacizumab in opposing MAPF-induced angiogenesis. In lung adenocarcinoma patients with malignant pleural effusion (MPE), Kaplan–Meier analysis revealed the benefit of cotreatment with target therapy and bevacizumab. Increased EGFR expression was observed in the pleural microvessels of patients with lung adenocarcinoma both with and without mutations in EGFR. MAPF was obtained from lung adenocarcinoma patients both wild-type and mutant EGFRs. Total and phosphorylated EGFR were upregulated in HUVEC cultured with MAPF. Treatment with gefitinib as an EGFR inhibitor suppressed MAPF-induced endothelial migration and partially attenuated endothelial proliferation in both wild-type and mutant EGFR lung adenocarcinoma. Cotreatment with gefitinib and bevacizumab produced better inhibition of MAPF-induced endothelial angiogenesis than gefitinib alone in the mutant EGFR subgroup. Protein analysis of MAPF-derived exosomes revealed abundant EGFR and p-EGFR components that implied possible transfer to endothelial cells. Concluding Kaplan–Meier analysis and in vitro studies, the results indicated that the addition of bevacizumab on gefitinib treatment could suppress MAPF-induced angiogenesis in lung adenocarcinoma patients.https://www.mdpi.com/2227-9059/9/10/1327lung cancermalignant associated pleural effusionvascular endotheliumEGFRgefitinibbevacizumab |
| spellingShingle | Wei-Teing Chen Yu-Huei Lin Chih-Ying Changchien Ying Chen Hsin-Han Chang Wen-Chiuan Tsai Hao-Chung Tsai Chieh-Yung Wang Ming-Sheng Shen Li-Ting Cheng Chen-Liang Tsai Concurrent Blockade of Endothelial EGFR and VEGF Signaling on Malignant Associated Pleural Fluid Induced Angiogenesis: From Clinic to Bench Biomedicines lung cancer malignant associated pleural effusion vascular endothelium EGFR gefitinib bevacizumab |
| title | Concurrent Blockade of Endothelial EGFR and VEGF Signaling on Malignant Associated Pleural Fluid Induced Angiogenesis: From Clinic to Bench |
| title_full | Concurrent Blockade of Endothelial EGFR and VEGF Signaling on Malignant Associated Pleural Fluid Induced Angiogenesis: From Clinic to Bench |
| title_fullStr | Concurrent Blockade of Endothelial EGFR and VEGF Signaling on Malignant Associated Pleural Fluid Induced Angiogenesis: From Clinic to Bench |
| title_full_unstemmed | Concurrent Blockade of Endothelial EGFR and VEGF Signaling on Malignant Associated Pleural Fluid Induced Angiogenesis: From Clinic to Bench |
| title_short | Concurrent Blockade of Endothelial EGFR and VEGF Signaling on Malignant Associated Pleural Fluid Induced Angiogenesis: From Clinic to Bench |
| title_sort | concurrent blockade of endothelial egfr and vegf signaling on malignant associated pleural fluid induced angiogenesis from clinic to bench |
| topic | lung cancer malignant associated pleural effusion vascular endothelium EGFR gefitinib bevacizumab |
| url | https://www.mdpi.com/2227-9059/9/10/1327 |
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