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Inhibition of LPS-mediated TLR4 activation abrogates gastric adenocarcinoma-associated peritoneal metastasis.
Sangwan, Veena; Al-Marzouki, Luai; Pal, Sanjima; Stavrakos, Vivian; Alzahrani, Malak; Antonatos, Dorothy; Nevo, Yehonatan; Camilleri-Broët, Sophie; Rayes, Roni; Bourdeau, France; Giannias, Betty; Bertos, Nicholas; Bailey, Swneke; Rousseau, Simon; Cools-Lartigue, Jonathan; Spicer, Jonathan D; Ferri, Lorenzo.
Afiliación
  • Sangwan V; Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, Canada.
  • Al-Marzouki L; Research Institute - McGill University Health Centre, Montreal, Canada.
  • Pal S; Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, Canada.
  • Stavrakos V; Research Institute - McGill University Health Centre, Montreal, Canada.
  • Alzahrani M; Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, Canada.
  • Antonatos D; Research Institute - McGill University Health Centre, Montreal, Canada.
  • Nevo Y; Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, Canada.
  • Camilleri-Broët S; Research Institute - McGill University Health Centre, Montreal, Canada.
  • Rayes R; Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, Canada.
  • Bourdeau F; Research Institute - McGill University Health Centre, Montreal, Canada.
  • Giannias B; Department of Pathology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
  • Bertos N; Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, Canada.
  • Bailey S; Research Institute - McGill University Health Centre, Montreal, Canada.
  • Rousseau S; Division of Thoracic Surgery, Department of Surgery, McGill University, Montreal, Quebec, Canada.
  • Cools-Lartigue J; Research Institute - McGill University Health Centre, Montreal, Canada.
  • Spicer JD; Department of Pathology, McGill University, Montreal, Quebec, Canada.
  • Ferri L; Research Institute - McGill University Health Centre, Montreal, Canada.
Clin Exp Metastasis ; 39(2): 323-333, 2022 04.
Article en En | MEDLINE | ID: mdl-34767138
Surgical resection, the cornerstone of curative intent treatment for gastric adenocarcinoma, is associated with a high rate of infection-related post-operative complications, leading to an increased incidence of metastasis to the peritoneum. However, the mechanisms underlying this process are poorly understood. Lipopolysaccharide (LPS), an antigen from Gram-negative bacteria, represents a potential mechanism via induction of local and systemic inflammation through activation of Toll-like receptor (TLR). Here, we use both a novel ex vivo model of peritoneal metastasis and in vivo animal models to assess gastric cancer cell adhesion to peritoneum both before and after inhibition of the TLR4 pathway. We demonstrate that activation of TLR4 by either LPS or Gram-negative bacteria (E. coli) significantly increases the adherence of gastric cancer cells to human peritoneal mesothelial cells, and that this increased adherence is abrogated by inhibition of the TLR4 signal cascade and downstream TAK1 and MEK1/2 pathways. We also demonstrate that the influence of LPS on adherence extends to peritoneal tissue and metastatic spread. Furthermore, we show that loss of TLR4 at the site of metastasis reduces tumor cell adhesion, implicating the TLR4 signaling cascade in potentiating metastatic adhesion and peritoneal spread. These results identify potential therapeutic targets for the clinical management of patients undergoing resection for gastric cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Peritoneales / Neoplasias Gástricas / Adenocarcinoma Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Clin Exp Metastasis Asunto de la revista: NEOPLASIAS Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Peritoneales / Neoplasias Gástricas / Adenocarcinoma Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Clin Exp Metastasis Asunto de la revista: NEOPLASIAS Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Países Bajos