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Interacção bactéria-hospedeiro na cancerização humana Infecção por Helicobacter pylori e cancro gástrico Céu Figueiredo.

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Presentation on theme: "Interacção bactéria-hospedeiro na cancerização humana Infecção por Helicobacter pylori e cancro gástrico Céu Figueiredo."— Presentation transcript:

1 Interacção bactéria-hospedeiro na cancerização humana Infecção por Helicobacter pylori e cancro gástrico Céu Figueiredo

2 H. pylori Chronic Superficial Gastritis Gastric Carcinoma Normal Gastric Mucosa Host susceptibility IL1B, IL1RN, TNFA genotypes Gastric carcinogenesis H. pylori strain virulence vacA s1m1, cagA+ Machado JC et al, Gastroenterology 2001 Machado JC et al, Gastroenterology 2003 Figueiredo C et al, Am J Pathol 2001 Figueiredo C et al, J Natl Cancer Inst 2002

3 cagA is part of a kb chromosomal region, the cag PAI, present in some but not all H. pylori strains The cag PAI encodes a type IV secretion system (T4SS) responsible for the translocation of bacterial molecules into the host cell cagA positive H. pylori strains are associated with more severe histopathologic features of chronic gastritis and increase the risk for gastric carcinoma development HP0520 HP0547 cagA cag PAI H. pylori cagA and cag pathogenicity island (cag PAI) Montecucco & Rappuoli, Nat Rev Mol Cell Biol 2001

4 Role of H. pylori virulence factors on epithelial cell responses and signaling pathways relevant to gastric carcinoma development

5 No. invasive cells * ** *Significantly different from untreated cells ** Significantly different from cells infected with H. pylori 60190wt H. pylori strains containing a functional cag pathogenicity island-encoded type IV secretion system (T4SS) stimulate gastric cancer cell invasion * To elucidate the effect of H. pylori on cell invasion

6 * Invasion index ** * Significantly different from untreated cells ** Significantly different from cells infected with H. pylori H. pylori strains containing a functional T4SS stimulate gastric cancer cell invasion, through a c-Met dependent signaling pathway Control * * ** No. invasive cells AGS + non-silenc. siRNA AGS + siRNA c-Met * Significantly different from untreated cells ** Significantly different from cells transfected with non-silencing siRNA To elucidate the signaling pathways involved in H. pylori-induced cell invasion

7 H. pylori strains containing a functional T4SS stimulate gastric cancer cell invasion, through a c-Met dependent signaling pathway To elucidate the signaling pathways involved in H. pylori-induced cell invasion

8 H. pylori strains containing a functional T4SS stimulate gastric cancer cell invasion, through a c-Met dependent signaling pathway, and involving an increase in MMP2 and MMP9 activity To elucidate the signaling pathways involved in H. pylori-induced cell invasion *Significantly different from untreated cells ** Significantly different from cells infected with H. pylori 60190wt

9 Conclusions –H. pylori strains containing a functional T4SS stimulate gastric cancer cell invasion, through a c-Met dependent signaling pathway, and involving an increase in MMP2 and MMP9 activity –These findings may implicate H. pylori at later stages of gastric carcinogenesis –If this is true, H. pylori eradication treatment should also be given to patients with dysplasia and early cancer

10 FP6, Integrated project INCA – The role of chronic infections in the development of cancer WP Leader: José Carlos Machado ERA-NET Pathogenomics HELDIVNET – Parasite and host genetic diversity in Helicobacter infections WP Leader: José Carlos Machado FP6, INCO Specific Measures CONTENT – Evaluation and Control of Neglected Mucosal Enteric Infections in Childhood WP Leader: José Carlos Machado ERA-NET Pathogenomics RNAi-NET – A global RNAi approach to unravel eukaryotic host functions that modulate bacterial infections WP Leader: Céu Figueiredo FCT - MCTES Effects of Helicobacter pylori on gastric epithelial cells PI: Céu Figueiredo

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