The sequential process prior to the appearance of a gastrointestinal tumour is histologically well-defined and starts with the colonisation of the gastric mucous by Helicobacter pylori; causing an inflammatory response that leads to chronic gastritis.
The inflammatory cells that infiltrate the mucous induce the expression of pro-inflammatory cytosines that may be responsible for the activation of genes involved in the neoplastic transformation of the gastric epithelium. The expression of intestinal markers is thus detected in the first stages of gastric carcinogenesis, such as intestinal metaplasia, and can be regulated by inflammatory cytosines.Our group is characterising the activation mechanisms of intestinal mucin genes (MUC2 and MUC4) by TNF-α, IL1-β and IL-6 in stomach cancer cells.
In neoplastic transformation, changes have been described in the glycosylation that alter the adhesion and invasion of the tumour cells, which facilitates the metastasis process. These changes can be partly induced by inflammatory cytosines, as they describe the activation of enzymes involved in glycosylation by TNF-α and IL-6. In order to analyse these changes, we are testing new glycosidic enzyme inhibitors that are fagomins, for gastric cancer cells and then determining their cytotoxic effects and the changes they induce in the glycosylation of proteins involved in the adhesion and invasion processes.
It is also important to evaluate is the relationship between inflammatory cells, specific gastrointestinal cancer markers and clinical pathologies of patients may have possible diagnostic and/or prognostic values.