Journal article
Lipopolysaccharide-induced toll-like receptor 4 signaling enhances the migratory ability of human esophageal cancer cells in a selectin-dependent manner
Surgery, Vol.154(1), pp.69-77
07/2013
DOI: 10.1016/j.surg.2013.03.006
PMID: 23809486
Abstract
Esophageal cancer is an aggressive malignancy, and emerging data suggest that postoperative infections may promote cancer progression. Systemic exposure to lipopolysaccharide (LPS), a Gram-negative bacterial antigen involved in such infections, has been shown to increase cancer cell adhesion to the hepatic sinusoids in vivo. We investigated the direct impact of LPS on the migratory ability of esophageal cancer cells via the LPS receptor toll-like receptor 4 (TLR4).
Human esophageal squamous carcinoma cell lines and immortalized normal esophageal mucosa cells were tested for TLR4 surface expression by reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry. TLR4 signaling in response to LPS stimulation was tested in these cells by measuring p38 MAP kinase phosphorylation on Western blot. The impact of TLR4 signaling was measured by static adhesion assays in vitro and on early in vivo migration by intravital microscopy of the liver.
Upon LPS stimulation, phosphorylation of p38 was detected in the human esophageal cancer cells HKESC-2. Also, LPS-stimulated HKESC-2 cells showed a twofold increased adhesion to fibronectin and to hepatic sinusoidal endothelium. These effects were abolished by TLR4 inhibition using the small-molecule inhibitor eritoran. Adhesion to fibronectin and hepatic sinusoidal endothelium was also diminished by blockade of p38 phosphorylation and inhibitors of selectin-selectin ligand binding.
LPS can increase the migratory ability of human esophageal cancer cells by increasing their adhesive properties through TLR4 signaling and selectin ligands. TLR4, p38, and selectin blockade may therefore prove to be a new therapeutic strategy for this aggressive malignancy.
Details
- Title: Subtitle
- Lipopolysaccharide-induced toll-like receptor 4 signaling enhances the migratory ability of human esophageal cancer cells in a selectin-dependent manner
- Creators
- Mathieu C Rousseau - LD McLean Surgical Research Laboratories, Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, CanadaRich Y.C Hsu - LD McLean Surgical Research Laboratories, Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, CanadaJonathan D Spicer - LD McLean Surgical Research Laboratories, Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, CanadaBraedon McDonald - LD McLean Surgical Research Laboratories, Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, CanadaCarlos H.F Chan - LD McLean Surgical Research Laboratories, Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, CanadaRushika M Perera - LD McLean Surgical Research Laboratories, Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, CanadaBetty Giannias - LD McLean Surgical Research Laboratories, Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, CanadaSimon C Chow - LD McLean Surgical Research Laboratories, Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, CanadaSimon Rousseau - Meakins-Christie Laboratories, McGill University Health Centre Research Institute, Department of Medicine, Montreal, Quebec, CanadaSimon Law - Department of Surgery, Division of Esophageal and Upper Gastrointestinal Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, ChinaLorenzo E Ferri - LD McLean Surgical Research Laboratories, Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, Canada
- Resource Type
- Journal article
- Publication Details
- Surgery, Vol.154(1), pp.69-77
- Publisher
- Mosby, Inc
- DOI
- 10.1016/j.surg.2013.03.006
- PMID
- 23809486
- ISSN
- 0039-6060
- eISSN
- 1532-7361
- Grant note
- Canadian Institutes of Health Research McGill University Health Centre Research Institute Canadian Cancer Society McGill Integrated Cancer Research Training Program Fonds de la recherche en santé du Québec
- Language
- English
- Date published
- 07/2013
- Academic Unit
- Surgery; Radiation Oncology
- Record Identifier
- 9984047658702771
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