Protumorigenic Responses of CEACAM6 in Helicobacter pylori-Infected Gastric Cancer Cells.

Helicobacter pylori poses a significant risk for gastric cancer (GC) development. H. pylori exploits carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) on GC cells (GCCs) to colonise the gastric epithelium. CEACAM1, CEACAM5 and CEACAM6 are known to interact with H. pylori. We explored the role of H. pylori in altering CEACAM levels in GCCs and the paracrine effect of infected GCCs on neighbouring uninfected GCCs and macrophages. H. pylori significantly upregulated CEACAM6. Elevated CEACAM6 in GCCs promoted cell proliferation, cell migration and cell invasion. The effect was further enhanced after infection with H. pylori. Similarly, soluble factors released by CEACAM6-transfected GCCs promoted the tumorigenic potential of uninfected GCCs. Macrophages are crucial for GC development and progression. Therefore, it was intriguing to know how CEACAM6 could influence the polarisation of macrophages during H. pylori infection. To study this, we co-cultured macrophages with either the empty vector or CEACAM6-expressing GCCs and found that H. pylori infection increased the M2 polarisation of macrophages co-incubated with CEACAM6-expressing GCCs. In summary, CEACAM6 was found to promote GC aggressiveness and alter macrophage polarisation. This information could be harnessed to develop future therapeutics for targeting GC.