Periostin mediates the increased pro-angiogenic activity of gastric cancer cells under hypoxic conditions.

This study was conducted to investigate the biological role of periostin in gastric cancer (GC) under hypoxia. Western blot analysis revealed that along with an upregulation of hypoxia-inducible factor-1alpha, there was a time-dependent induction of periostin in MKN-45 cells under hypoxia (2% O2 ), increasing by eightfold as compared to normoxic cells. Pretreatment with 30 µM PD98059, an inhibitor of ERK1/2, significantly reduced hypoxia-stimulated periostin expression (P < 0.01). Periostin knockdown in MKN-45 cells was achieved by specific small interfering RNA (siRNA). The conditioned medium from periostin siRNA-transfected MKN-45 cells induced significantly less (P < 0.01) endothelial tube formation than control siRNA-transfected cells. Additionally, periostin silencing markedly decreased the mRNA expression and secretion of vascular endothelial growth factor (VEGF) in hypoxic MKN-45 cells. Thus, our data suggest that periostin is a hypoxia-response gene and mediates a cross talk between GC and endothelial cells under hypoxia, partially through regulation of the VEGF expression.