New Target Genes for Tumor-derived Soluble Factors in Primary Monocytes

Abstract

Background: Tumor cells have developed several strategies to escape the immune system. One of these strategies consists of the secretion of immunosuppressive factors like interleukin-10 or prostaglandin E2 (PGE₂), which impair the immune system. We have demonstrated recently that tumor-derived PGE₂ down-regulates the expression of the integrin Mac-1 and the chemokine receptor CCR5 on primary monocytes, resulting in reduced adhesion and migration. Materials and Methods: In order to identify new target genes for tumor-derived factors in monocytes, we set up an in vitro system consisting of cDNA micro arrays and 2D gel electrophoresis. Results: We identified 25 genes that were differentially expressed upon incubation of cells in conditioned tumor cell supernatants as compared to cells incubated in cell culture medium. We describe in more detail that IL-1β secretion is induced by tumor supernatants and that IL-1β overexpression is also evident in monocytes from tumor patients in vivo, where expression correlates with the tumor stage. In addition, up-regulation of the plasminogen activator inhibitor-2, PAI-2, and down-regulation of the urokinase-type plasminogen activator receptor, uPAR, resulted in a reduced capability of monocytes to degrade and invade extracellular matrices. Conclusion: In summary, we describe interesting novel targets of soluble tumor-derived factors that are probably involved in the tumor-mediated immunosuppression commonly found in cancer patients.