Int J Biol Sci 2019; 15(10):2110-2118. doi:10.7150/ijbs.31605

Research Paper

Extracellular Vesicles (EVs) from Lung Adenocarcinoma Cells Promote Human Umbilical Vein Endothelial Cell (HUVEC) Angiogenesis through Yes Kinase-associated Protein (YAP) Transport

Ying Wang1, Liyang Dong2, Hai Zhong3, Linfei Yang1, Qian Li1, Chuan Su4✉, Wei Gu1✉, Yingying Qian1✉

1. Department of Respiration, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, Jiangsu 210006, People' s Republic of China
2. Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu 212002, People' s Republic of China
3. Department of Respiration, Jiangning Hospital, Nanjing Medical University, 168 Gushan Road, Nanjing, Jiangsu 211101, People' s Republic of China
4. Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, Center for Global Health, Nanjing Medical University, Nanjing, Jiangsu 211166, People's Republic of China

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Citation:
Wang Y, Dong L, Zhong H, Yang L, Li Q, Su C, Gu W, Qian Y. Extracellular Vesicles (EVs) from Lung Adenocarcinoma Cells Promote Human Umbilical Vein Endothelial Cell (HUVEC) Angiogenesis through Yes Kinase-associated Protein (YAP) Transport. Int J Biol Sci 2019; 15(10):2110-2118. doi:10.7150/ijbs.31605. Available from http://www.ijbs.com/v15p2110.htm

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Abstract

Yes kinase-associated protein (YAP) plays an important role in angiogenesis and can promote the occurrence and development of many tumor types. However, whether YAP affects tumor angiogenesis in lung cancer, and its potential mechanism in lung cancer, are unknown. In this study, we explored the role of YAP in the angiogenesis of lung adenocarcinoma, and further illustrated its possible mechanism. The expression levels of YAP and the vascular endothelial marker protein CD31 were examined by immunohistochemistry and immunofluorescence in human lung adenocarcinoma tissues, revealing a possible positive correlation between YAP and CD31 in lung adenocarcinoma. The results of the western blotting (WB) of Human Umbilical Vein Endothelial Cells (HUVECs) after coculture with lung adenocarcinoma H1975 cells, H1975 cell-supernatants and H1975-derived EVs showed that YAP derived from H1975 cells can enter HUVECs via EVs. These results were confirmed by immunofluorescence. Finally, we generated H1975 low-YAP expression cells by transfecting the cells with a shYAP lentivirus, and confirmed that the low expression of YAP in H1975 cells inhibits HUVEC angiogenesis by reducing the amount of YAP that enters HUVECs. We found, for the first time, that YAP promotes angiogenesis in lung adenocarcinoma via EVs, at least partially. Our work may provide a promising method for lung cancer treatment by targeting angiogenesis in the future.

Keywords: YAP, lung adenocarcinoma, H1975 cell, EVs, angiogenesis