Interleukin-1α enhances angiogenesis and is associated with liver metastatic potential in human gastric cancer cell lines

Background. To better understand the underlying mechanism of liver metastasis formation in human gastric cancer, we evaluated the angiogenic capabilities of human gastric cancer cell lines with different metastatic potentials as well as the role of interleukin (IL)-1 alpha in the angiogenic process. Materials and methods. Reverse transcription-polymerase chain reaction was used to detect the expression of IL-1 alpha and vascular endothelial growth factor (VEGF) mRNA in gastric cancer cell lines with different liver metastatic potentials. Levels of VEGF secreted by human gastric cancer cells were measured by enzyme-linked immunosorbent assay. We also examined how gastric cancer cells with different metastatic potentials influence the proliferation and tube formation of human umbilical vein endothelial cells (HU-VECs) using the Premix WST-1 cell proliferation assay system and an angiogenesis assay, respectively. Results. IL-1 alpha expression levels were significantly correlated with liver metastatic potential in gastric cancer cell lines. Levels of VEGF secreted by gastric cancer cells appear to be regulated by IL-1 alpha through IL-1 receptor Type 1 and were correlated with liver metastatic potential. Both HUVEC proliferation and tube formation were strongly enhanced by coculture with high liver-metastatic gastric cancer cells and were enhanced to a similar extent by culture in the presence of IL-1 alpha. In contrast, blockade of IL-1 alpha inhibited both HUVEC proliferation and angiogenesis. Conclusions. IL-1 alpha may play a role in liver metastasis of gastric cancer via enhanced vascular endothelial cell proliferation and angiogenesis. (C) 2008 Elsevier Inc. All rights reserved.