Concurrent blockade of endothelial egfr and vegf signaling on malignant associated pleural fluid induced angiogenesis: From clinic to bench

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

研究成果: 雜誌貢獻文章同行評審

摘要

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.

原文英語
文章編號1327
期刊Biomedicines
9
發行號10
DOIs
出版狀態已發佈 - 十月 2021

ASJC Scopus subject areas

  • 醫藥(雜項)
  • 生物化學、遺傳與分子生物學 (全部)

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