Helicobacter pylori-induced exosomal MET educates tumour-associated macrophages to promote gastric cancer progression

Journal of Cellular and Molecular Medicine
Ying CheQiang You

Abstract

Helicobacter pylori (H. pylori) infection triggers chronic inflammation that has been associated with gastric cancer (GC). Exosomes are small extracellular vesicles that have become the key mediators of intercellular communication. In this study, we investigated exosome-mediated communication between H. pylori-infected GC cells and macrophages, focusing on the transfer of activated mesenchymal-epithelial transition factor (MET). We observed a significant decrease in MET protein expression in GC cells after infection with H. pylori, whereas MET mRNA levels remained unchanged. Intriguingly, MET expression, specifically the phosphorylated active form, was increased in exosomes released from H. pylori-infected GC cells. Confocal microscopy and Western blotting analyses showed that these exosomes containing MET were delivered to and internalized by macrophages. Indeed, in human GC tissues positive for H. pylori, we also observed that activated MET was highly expressed in tumour-infiltrating macrophages. After internalization, exosomal MET then appeared to educate the macrophages towards a pro-tumorigenesis phenotype. This included exosomal MET-mediated stimulation of proinflammatory cytokine secretion IL-1β, which subsequently promo...Continue Reading

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Mar 17, 2019·Molecular Cancer·Min FuXu Zhang
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Methods Mentioned

BETA
Protein Assay
transmission electron microscopy
PCR
ELISA
xenografts
transfect
confocal microscopy
xenograft

Software Mentioned

Image J

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