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Title: Toll-like receptor 4 promotes angiogenesis in pancreatic cancer via PI3K/AKT signaling

Abstract

Deregulation of Toll-like receptor 4 (TLR4) is closely associated with the progression of various types of cancers, but its role in pancreatic carcinogenesis is unclear. This study aimed to investigate the role of TLR4 in the angiogenesis of pancreatic cancer and the underlying molecular mechanisms. The culture supernatant (conditioned medium) of PANC-1 cells after appropriate treatment was used for the treatment of HUVECs. The proliferation, migration and tube formation of HUVECs were assessed by MTT, Transwell and Matrigel, respectively. In pancreatic cancer tissues, TLR4, VEGF and CD31 were upregulated as determined by immunohistochemistry and the expression of TLR4 and VEGF was positively correlated with microvessel density as detected by CD31 staining. Activation of TLR4 signaling by LPS in PANC-1 cells resulted in increased VEGF and phosphorylation of AKT, which were abolished by TLR4 silencing with siRNA and PI3K/AKT signaling inhibitor LY294002. The conditioned medium from PANC-1 cells treated with LY294002 or transfected with TRL4 siRNA reduced the proliferation, migration and tube formation of HUVECs. In contrast, the conditioned medium from PANC-1 cells treated with LPS stimulated the proliferation, migration and tube formation of HUVECs, which was however significantly inhibited by pretreatment of PANC-1 cells with LY294002 or transfection with TRL4more » siRNA. Our findings suggest TLR4 may promote angiogenesis in pancreatic cancer by activating the PI3K/AKT signaling pathway to induce VEGF expression.« less

Authors:
;  [1];  [2];  [2]; ; ;  [3]
  1. Department of Gastroenterology, Lianyungang Ganyu People’s Hospital, Ganyu, Jiangsu (China)
  2. Department of Gastroenterology, Huadong Hospital, Fudan University, Shanghai (China)
  3. Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai (China)
Publication Date:
OSTI Identifier:
22649764
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 347; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANGIOGENESIS; CARCINOGENESIS; CATTLE; DENSITY; DMSO; ENZYME IMMUNOASSAY; ENZYMES; GROWTH FACTORS; LIPOPOLYSACCHARIDES; NEOPLASMS; PANCREAS; PHOSPHORYLATION; PLANT GROWTH; PLANT TISSUES; RECEPTORS; SIGNALS; VEINS

Citation Formats

Sun, Yunliang, Wu, Congshan, Ma, Jianxia, E-mail: yz_mjx@163.com, Yang, Yu, Man, Xiaohua, Wu, Hongyu, and Li, Shude. Toll-like receptor 4 promotes angiogenesis in pancreatic cancer via PI3K/AKT signaling. United States: N. p., 2016. Web. doi:10.1016/J.YEXCR.2016.07.009.
Sun, Yunliang, Wu, Congshan, Ma, Jianxia, E-mail: yz_mjx@163.com, Yang, Yu, Man, Xiaohua, Wu, Hongyu, & Li, Shude. Toll-like receptor 4 promotes angiogenesis in pancreatic cancer via PI3K/AKT signaling. United States. doi:10.1016/J.YEXCR.2016.07.009.
Sun, Yunliang, Wu, Congshan, Ma, Jianxia, E-mail: yz_mjx@163.com, Yang, Yu, Man, Xiaohua, Wu, Hongyu, and Li, Shude. Sat . "Toll-like receptor 4 promotes angiogenesis in pancreatic cancer via PI3K/AKT signaling". United States. doi:10.1016/J.YEXCR.2016.07.009.
@article{osti_22649764,
title = {Toll-like receptor 4 promotes angiogenesis in pancreatic cancer via PI3K/AKT signaling},
author = {Sun, Yunliang and Wu, Congshan and Ma, Jianxia, E-mail: yz_mjx@163.com and Yang, Yu and Man, Xiaohua and Wu, Hongyu and Li, Shude},
abstractNote = {Deregulation of Toll-like receptor 4 (TLR4) is closely associated with the progression of various types of cancers, but its role in pancreatic carcinogenesis is unclear. This study aimed to investigate the role of TLR4 in the angiogenesis of pancreatic cancer and the underlying molecular mechanisms. The culture supernatant (conditioned medium) of PANC-1 cells after appropriate treatment was used for the treatment of HUVECs. The proliferation, migration and tube formation of HUVECs were assessed by MTT, Transwell and Matrigel, respectively. In pancreatic cancer tissues, TLR4, VEGF and CD31 were upregulated as determined by immunohistochemistry and the expression of TLR4 and VEGF was positively correlated with microvessel density as detected by CD31 staining. Activation of TLR4 signaling by LPS in PANC-1 cells resulted in increased VEGF and phosphorylation of AKT, which were abolished by TLR4 silencing with siRNA and PI3K/AKT signaling inhibitor LY294002. The conditioned medium from PANC-1 cells treated with LY294002 or transfected with TRL4 siRNA reduced the proliferation, migration and tube formation of HUVECs. In contrast, the conditioned medium from PANC-1 cells treated with LPS stimulated the proliferation, migration and tube formation of HUVECs, which was however significantly inhibited by pretreatment of PANC-1 cells with LY294002 or transfection with TRL4 siRNA. Our findings suggest TLR4 may promote angiogenesis in pancreatic cancer by activating the PI3K/AKT signaling pathway to induce VEGF expression.},
doi = {10.1016/J.YEXCR.2016.07.009},
journal = {Experimental Cell Research},
number = 2,
volume = 347,
place = {United States},
year = {Sat Oct 01 00:00:00 EDT 2016},
month = {Sat Oct 01 00:00:00 EDT 2016}
}