Biophysical Properties and Motility of Human Mature Dendritic Cells Deteriorated by Vascular Endothelial Growth Factor through Cytoskeleton Remodeling.
Dendritic cells (DCs), the most potent antigen-presenting cells, play a central role in the initiation, regulation, and maintenance of the immune responses. Vascular endothelial growth factor (VEGF) is one of the important cytokines in the tumor microenvironment (TME) and can inhibit the differentiation and functional maturation of DCs. To elucidate the potential mechanisms of DC dysfunction induced by VEGF, the effects of VEGF on the biophysical characteristics and motility of human mature DCs (mDCs) were investigated. The results showed that VEGF had a negative influence on the biophysical properties, including electrophoretic mobility, osmotic fragility, viscoelasticity, and transmigration. Further cytoskeleton structure analysis by confocal microscope and gene expression profile analyses by gene microarray and real-time PCR indicated that the abnormal remodeling of F-actin cytoskeleton may be the main reason for the deterioration of biophysical properties, motility, and stimulatory capability of VEGF-treated mDCs. This is significant for understanding the biological behavior of DCs and the immune escape mechanism of tumors. Simultaneously, the therapeutic efficacies may be improved by blocking the signaling pathway of VEGF in an appropriate manner before the deployment of DC-based vaccinations against tumors.
Key Laboratory of Biological and Medical Engineering, Guizhou Medical University, Guiyang 550025, China. huzuquan@gmc.edu.cn.|Engineering Research Center of Medical Biotechnology, Guizhou Medical University, Guiyang 550025, China. huzuquan@gmc.edu.cn.|School of Biology and Engineering, Guizhou Medical University, Guiyang 550025, China. huzuquan@gmc.edu.cn.
Zu-Quan
ZQ
Hu
Key Laboratory of Biological and Medical Engineering, Guizhou Medical University, Guiyang 550025, China. xuehui@bjmu.edu.cn.|Engineering Research Center of Medical Biotechnology, Guizhou Medical University, Guiyang 550025, China. xuehui@bjmu.edu.cn.|School of Biology and Engineering, Guizhou Medical University, Guiyang 550025, China. xuehui@bjmu.edu.cn.
Hui
H
Xue
Department of Head and Neck, Affiliated Cancer Hospital, Guizhou Medical University, Guiyang 550025, China. longjinhua100@sina.cn.
Jin-Hua
JH
Long
Key Laboratory of Biological and Medical Engineering, Guizhou Medical University, Guiyang 550025, China. wangyun@gmc.edu.cn.|Engineering Research Center of Medical Biotechnology, Guizhou Medical University, Guiyang 550025, China. wangyun@gmc.edu.cn.|School of Biology and Engineering, Guizhou Medical University, Guiyang 550025, China. wangyun@gmc.edu.cn.
Yun
Y
Wang
Key Laboratory of Biological and Medical Engineering, Guizhou Medical University, Guiyang 550025, China. jiayiyouxiang@163.com.|Engineering Research Center of Medical Biotechnology, Guizhou Medical University, Guiyang 550025, China. jiayiyouxiang@163.com.|School of Biology and Engineering, Guizhou Medical University, Guiyang 550025, China. jiayiyouxiang@163.com.
Yi
Y
Jia
Key Laboratory of Biological and Medical Engineering, Guizhou Medical University, Guiyang 550025, China. qwei407@163.com.|Engineering Research Center of Medical Biotechnology, Guizhou Medical University, Guiyang 550025, China. qwei407@163.com.|School of Biology and Engineering, Guizhou Medical University, Guiyang 550025, China. qwei407@163.com.
Wei
W
Qiu
Key Laboratory of Biological and Medical Engineering, Guizhou Medical University, Guiyang 550025, China. zhou323jing126@126.com.|Engineering Research Center of Medical Biotechnology, Guizhou Medical University, Guiyang 550025, China. zhou323jing126@126.com.|School of Biology and Engineering, Guizhou Medical University, Guiyang 550025, China. zhou323jing126@126.com.
Jing
J
Zhou
Hemorheology Center, School of Basic Medical Sciences, Health Science Center of Peking University, Beijing 100191, China. rheol@bjmu.edu.cn.
Zong-Yao
ZY
Wen
Hemorheology Center, School of Basic Medical Sciences, Health Science Center of Peking University, Beijing 100191, China. ywj01@hotmail.com.
Wei-Juan
WJ
Yao
Key Laboratory of Biological and Medical Engineering, Guizhou Medical University, Guiyang 550025, China. zengzhu100@sina.com.|Engineering Research Center of Medical Biotechnology, Guizhou Medical University, Guiyang 550025, China. zengzhu100@sina.com.|School of Biology and Engineering, Guizhou Medical University, Guiyang 550025, China. zengzhu100@sina.com.
Zhu
Z
Zeng
D000199:Actins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D055592:Biophysical Phenomena / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004548:Elasticity; D004586:Electrophoresis; D020869:Gene Expression Profiling; D063990:Gene Ontology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009996:Osmotic Fragility / Q000187:drug effects; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D014783:Viscosity
D000199:Actins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A
biophysical characteristics; dendritic cells; immune function; motility; vascular endothelial growth factor