Stanniocalcin-1 promotes tumor angiogenesis through up-regulation of VEGF in gastric cancer cells

BGC/STC cells (high-expression of STC-1) and BGC/shSTC cells (low- expression of STC-1) were constructed to investigate the effect of STC-1 on the xenograft tumor growth and angiogenesis in vitro and in vivo. ELISA assay was used to detect the expression of vascular endothelial growth factor (VEGF) in the supernatants. Neutralizing antibody was used to inhibit VEGF expression in supernatants. The expression of phosphorylated -PKCβII, phosphorylated -ERK1/2 and phosphorylated -P38 in the BGC treated with STC-1protein was detected by western blot.STC-1 could promote angiogenesis in vitro and in vivo, and the angiogenesis was consistent with VEGF expression in vitro. Inhibition of VEGF expression in supernatants with neutralizing antibody markedly abolished angiogenesis induced by STC-1 in vitro. The process of STC-1-regulated VEGF expression was mediated via PKCβII and ERK1/2.STC-1 promotes the expression of VEGF depended on the activation of PKCβII and ERK1/2 pathways. VEGF subsequently enhances tumor angiogenesis which in turn promotes the gastric tumor growth.Development of gastric cancer involves multiple factor changes that lead to the transformation of human gastric epithelial cells to gastric cancer cells [1]. Angiogenesis is a critical hallmark of malignancy and can occur at different stages of the tumor progression [2]. Acquisition of the angiogenic phenotype can result from genetic changes or local environmental changes such as the secretion of pro-angiogenic growth factors by tumor that lead to the activation of endothelial cells. Stanniocalcin-1(STC-1) is a glycoprotein hormone originally discovered in the corpuscles of Stannius of bony fish [3]. The expression of the mammalian STC-1 was found in numerous developmental and pathophysiological processes [4-8]. Growing evidence suggests that the mammalian STC-1 may be associated with carcinogenesis. Aberrant STC-1 expression has been reported in breast and ovarian cancers [9-11]. Our previous study found that