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

Sun, Yunliang; Wu, Congshan; Ma, Jianxia; Yang, Yu; Man, Xiaohua; Wu, Hongyu; Li, Shude

doi:10.1016/J.YEXCR.2016.07.009

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

Full Record
Other Related Research

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 »« less

Authors:

Sun, Yunliang; Wu, Congshan ^[1]; Ma, Jianxia ^[2]; Yang, Yu ^[2]; Man, Xiaohua; Wu, Hongyu; Li, Shude ^[3]

Department of Gastroenterology, Lianyungang Ganyu People’s Hospital, Ganyu, Jiangsu (China)
Department of Gastroenterology, Huadong Hospital, Fudan University, Shanghai (China)
Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai (China)

Publication Date:: Sat Oct 01 00:00:00 EDT 2016

OSTI Identifier:: 22649764

Resource Type:: Journal Article

Journal Name:: Experimental Cell Research

Additional Journal Information:: 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); Journal ID: ISSN 0014-4827

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, 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.

Copy to clipboard


                    Sun, Yunliang, Wu, Congshan, Ma, Jianxia, Yang, Yu, Man, Xiaohua, Wu, Hongyu, & Li, Shude. Toll-like receptor 4 promotes angiogenesis in pancreatic cancer via PI3K/AKT signaling.  United States.  https://doi.org/10.1016/J.YEXCR.2016.07.009

Copy to clipboard


                    Sun, Yunliang, Wu, Congshan, Ma, Jianxia, Yang, Yu, Man, Xiaohua, Wu, Hongyu, and Li, Shude. 2016.  
        "Toll-like receptor 4 promotes angiogenesis in pancreatic cancer via PI3K/AKT signaling".  United States.  https://doi.org/10.1016/J.YEXCR.2016.07.009.

Copy to clipboard


                    
@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 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},

  url          = {https://www.osti.gov/biblio/22649764},
  journal      = {Experimental Cell Research},

  issn         = {0014-4827},

  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}

}

Copy to clipboard

Journal Article:

https://doi.org/10.1016/J.YEXCR.2016.07.009

Other availability

Find in Google Scholar

Search WorldCat to find libraries that may hold this journal

Save / Share:

Export Metadata

Save to My Library

Similar records in OSTI.GOV collections:

Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer

Journal Article Yu, Wei; Chai, Hongyan; Li, Ying; ... - Toxicology and Applied Pharmacology

Cytochrome P450 (CYP) 4Z1, a novel CYP4 family member, is over-expressed in human mammary carcinoma and associated with high-grade tumors and poor prognosis. However, the precise role of CYP4Z1 in tumor progression is unknown. Here, we demonstrate that CYP4Z1 overexpression promotes tumor angiogenesis and growth in breast cancer. Stable expression of CYP4Z1 in T47D and BT-474 human breast cancer cells significantly increased mRNA expression and production of vascular endothelial growth factor (VEGF)-A, and decreased mRNA levels and secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2), without affecting cell proliferation and anchorage-independent cell growth in vitro. Notably, the conditioned medium from CYP4Z1-expressingmore »« less
https://doi.org/10.1016/J.TAAP.2012.07.019
Placental growth factor enhances angiogenesis in human intestinal microvascular endothelial cells via PI3K/Akt pathway: Potential implications of inflammation bowel disease

Journal Article Zhou, Yi; Tu, Chuantao; Zhao, Yuan; ... - Biochemical and Biophysical Research Communications

Background: Angiogenesis plays a major role in the pathogenesis of inflammatory bowel disease (IBD). Placental growth factor (PlGF) is a specific regulator of pathological angiogenesis and is upregulated in the sera of IBD patients. Therefore, the role of PlGF in IBD angiogenesis was investigated here using HIMECs. Methods: The expression of PlGF and its receptors in human intestinal microvascular endothelial cells (HIMECs) and inflamed mucosa of IBD patients were examined using quantitative PCR and western blot analysis and the role of PlGF in IBD HIMECs was further explored using small interfering RNA (siRNA). The induction of pro-inflammatory cytokine by PlGFmore »« less
https://doi.org/10.1016/J.BBRC.2016.01.073
VEGF111b, a new member of VEGFxxxb isoforms and induced by mitomycin C, inhibits angiogenesis

Journal Article Gu, Fang; Li, Xiuli; Kong, Jian; ... - Biochemical and Biophysical Research Communications

Highlights: •We discovered a new member of VEGFxxxb family-VEGF111b. •We found VEGF111b mRNA and protein can be induced by mitomycin C. •We confirmed VEGF111b over-expression inhibits angiogenesis. •VEGF111b inhibits angiogenesis through inhibiting VEGF-R2/PI3K/Akt and VEGF-R2/ERK1/2 phosphorylation. -- Abstract: Vascular endothelial growth factor (VEGF-A) stimulating angiogenesis is required for tumor growth and progression. The conventional VEGF-A isoforms have been considered as pro-angiogenic factors. Another family of VEGF-A isoforms generated by alternative splicing, termed VEGFxxxb isoforms, has anti-angiogenic property, exemplified by VEGF165b. Here, we identify a new number of VEGFxxx family-VEGF111b induced by mitomycin C, although not detected in mitomycin C-unexposed ovarianmore »« less
https://doi.org/10.1016/J.BBRC.2013.09.144
1-o-acetylbritannilactone (ABL) inhibits angiogenesis and lung cancer cell growth through regulating VEGF-Src-FAK signaling

Journal Article Zhengfu, He; Hu, Zhang; Huiwen, Miao; ... - Biochemical and Biophysical Research Communications

The search for safe, effective and affordable therapeutics against non-small cell lung cancer (NSCLC) and other lung cancers is important. Here we explored the potential effect of 1-o-acetylbritannilactone (ABL), a novel extract from Inula britannica-F, on angiogenesis and lung cancer cell growth. We demonstrated that ABL dose-dependently inhibited vascular endothelial growth factor (VEGF)-induced proliferation, migration, and capillary structure formation of cultured human umbilical vascular endothelial cells (HUVECs). In vivo, ABL administration suppressed VEGF-induced new vasculature formation in Matrigel plugs. For the mechanism investigations, we found that ABL largely inhibited VEGF-mediated activation of Src kinase and focal adhesion kinase (FAK) in HUVECs.more »« less
https://doi.org/10.1016/J.BBRC.2015.06.126
OSU-A9 inhibits angiogenesis in human umbilical vein endothelial cells via disrupting Akt–NF-κB and MAPK signaling pathways

Journal Article Omar, Hany; Arafa, El-Shaimaa; Salama, Samir; ... - Toxicology and Applied Pharmacology

Since the introduction of angiogenesis as a useful target for cancer therapy, few agents have been approved for clinical use due to the rapid development of resistance. This problem can be minimized by simultaneous targeting of multiple angiogenesis signaling pathways, a potential strategy in cancer management known as polypharmacology. The current study aimed at exploring the anti-angiogenic activity of OSU-A9, an indole-3-carbinol-derived pleotropic agent that targets mainly Akt–nuclear factor-kappa B (NF-κB) signaling which regulates many key players of angiogenesis such as vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Human umbilical vein endothelial cells (HUVECs) were used to studymore »« less
https://doi.org/10.1016/J.TAAP.2013.07.014

Similar Records