Role of the protein CagA from Helicobacter pylori in the modifications of the human B lymphocyte cytoskeleton

Abstract

Abstract The cytotoxin-associated gen A (CagA) is an oncogenic virulence factor of Helicobacter pylori that is related with the development of gastric cancer and gastric MALToma: a B cell non-Hodgkin’s lymphoma. CagA has an important role in the development of cancer due to its promiscuous interaction with different signaling-mediators. The association of CagA with cytoskeleton regulators generates an effect that gives invasive characteristics to epithelial cells, thus explaining the evolution to late stages of the gastric carcinoma. Although the translocation of CagA has been demonstrated in B lymphocytes, its impact on MALToma development and its effects over B cell cytoskeleton have not been characterized. Human Raji B cells were transiently transfected to express an EGFP-tagged CagA fusion protein. In culture, these cells displayed altered morphological and adhesion properties when compared with control cells. Fibronectin induced-spreading and adhesion assays were performed to assess the changes observed. The transfected cells exhibited atypical size and shape descriptors, determined by analyses of confocal microscopy images. Concomitantly, the adhesion of CagA+ Raji cells was observed reduced. These phenotypes could be explained by the diminished basal levels of ezrin that we detect in the CagA+ cells, determined by Western blot, that contrast with a high expression of this actin-regulatory molecule in Raji control cells. Taken together, our results show that the expression of CagA produces important changes in B cell morphology as well as cell adhesion due to alteration in actin cytoskeleton regulation; changes that could explain an invasive and aggressive B lymphocyte profile.