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MAPK/ERK1/2 signaling mediates endothelial-like differentiation of immature DCs in the microenvironment of esophageal squamous cell carcinoma

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Abstract

Endothelial-like differentiation of dendritic cells (DCs) is a new phenomenon, and the mechanism is still elusive. Here, we show that the tumor microenvironment derived from the human esophageal squamous cell carcinoma (ESCC) cell line EC9706 can induce immature DCs (iDCs) differentiate toward endothelial cells, and become endothelial-like cells, but it has no obvious influence on mature DCs. During the course of endothelial-like differentiation of iDCs, a sustained activation of mitogen-activated protein kinase/extracelluar signal-regulated kinase1/2 (MAPK/ERK1/2) and cAMP response element-binding protein (CREB) was detected. Incubation of iDCs with MEK phosphorylation inhibitor PD98059 blocked the MAPK/ERK1/2 and CREB phosphorylation as well as the endothelial-like differentiation of iDCs. Inhibition of vascular endothelial growth factor-A (VEGF-A) in the microenvironment with its antibody blocked the endothelial-like differentiation and the phosphorylation of MAPK/ERK1/2 and CREB. These data suggest that MAPK/ERK1/2 signaling pathway activated by VEGF-A could mediate endothelial-like differentiation of iDCs in the ESCC microenvironment.

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Acknowledgments

This work was supported by the Science and Technology Research Key Project of the Ministry of Education (No. 207150) and the Natural Science Foundation of the Henan Province of China (No. 20060011 and 2008A310018). We would like to express our thanks to the staff of the Open Laboratory of the Key Discipline of Molecular Medicine of the Henan Province and the Electron Microscopy Research Center of the Hebei Medical University for their helpful technical support, and thanks to Dr. Ziyou Cui and peer reviewers for critically reading the manuscript and giving good suggestions.

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  1. Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450052, China

    Jing Lu, Jimin Zhao, Kangdong Liu, Jun Zhao, Hongyan Yang, Youtian Huang, Zhenzhu Qin, Ruihua Bai, Pei Li, Junfen Ma, Wenhai Yan, Mingyao Zhao & Ziming Dong

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  1. Jing Lu
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Lu, J., Zhao, J., Liu, K. et al. MAPK/ERK1/2 signaling mediates endothelial-like differentiation of immature DCs in the microenvironment of esophageal squamous cell carcinoma. Cell. Mol. Life Sci. 67, 2091–2106 (2010). https://doi.org/10.1007/s00018-010-0316-8

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