Effect of Helicobacter pylori in the expression of angiogenic factors in isolated gastric cancer cells

Abstract

BACKGROUND: Angiogenesis is a complex process that provides tumoral cells with and adequate growth environment and plays a role in metastasis. Several studies have demonstrated the expression of some angiogenic factors, such as platelet-derived endothelial cell growth factor (PD-ECGF) and vascular growth factor (VEGF) in sub-sets of gastric carcinomas. Helicobacter pylori (H pylori) has been considered to be a risk factor for gastric cancer development. Whether H pylori infection influences the expression of PD-ECGF and VEGF in gastric epithelial cells has never been studied. AIM: to assess whether H pylori may affect the cellular pathways that lead to expression of angiogenic factors by gastric cancer cells. METHODS: The gastric cancer cell lines SNU 668, KATOIII, SNU 16 and SNU 638 were tested. The cells were co-cultured with H pylori (ATCC 43504) for 24 hours. Equal amounts(lO ug) of protein extracts were separated by SDS-PAGE and western blots were performed with PD-ECGF, VEGF and control actinspecific antibodies. Protein extracts from control cells cultured in the absence of H pylori were run in parallel. RESULTS: Expression of VEGF was detected in the four cancer cell lines while PD-ECGF protein was only detected in SNU 668 and SNU 638 cells. Co-culture with H pylori resulted in decreased protein levels of both PD-ECGF and VEGF factor. However, while the levels of VEGF decreased in the four cell lines tested, a drop in PD-ECGF levels was only detected in SNU 638 cells. In contrast. the levels of actin were similar in cells with or without exposure to H pylori. CONCLUSIONS: The angiogenic factors PD-ECGF and VEGF are expressed in various gastric cancer cell lines. The interaction of intact H pylori organisms with gastric cancer cells causes a reduction in VEGF and PD-ECGF protein levels. These findings provide additional evidence that H pylonbacterial products may affect gastric cell pathways in a direct manner, in the absence of inflammatory products. The biological implications of these effects in vivo may be of relevance to the understanding of H pylori-related gastric carcinogenesis. 5654