Cancer cell-derived IL-1alpha induces IL-8 release in endothelial cells

Abstract

PURPOSE: Cancer cells release a multitude of cytokines and growth factors that influence neighboring cells and help establish a favorable environment for tumor development. As part of our studies designed to elucidate the complex cellular interactions within the tumor microenvironment that facilitate tumor development, we investigated cancer cell-induced changes in gene expression in endothelial cells. METHODS: After treatment of human umbilical vein endothelial cells (HUVEC) with conditioned medium (CM) of SNUC5 colon cancer cells, gene expression profile in HUVEC was analyzed using cDNA microarray. Neutralizing antibodies against pro-inflammatory cytokines were used to identify the major effecter in SNUC5 CM. RESULTS: IL-8 was one of the four genes up-regulated over fourfold, and IL-1alpha in SNUC5 CM was revealed as a major effecter of IL-8 over-expression and release, which was nearly completely neutralized by anti-IL-1alpha antibody. Constitutive secretion of IL-1alpha was confirmed in many other human cancer cells. CONCLUSIONS: IL-1alpha is constitutively expressed in many human cancer cells and directly induces IL-8 secretion in neighboring endothelial cells.