Effects of Tumor Cell-Derived Interleukin 1 Alpha on Invasiveness of Metastatic Clones of Murine RCT Sarcoma through Endothelial Cells

Abstract

Interleukin 1 alpha (IL-1α) production and invasiveness through mouse lung endothelial cells (MLE) were investigated in high-metastatic RCT+ and low-metastatic RCT– clones established from poorly differentiated murine sarcoma. Apparently, a higher level of IL-1α was derived from RCT+ cells than from RCT– cells. In an invasion assay, the number of cells which penetrated the MLE monolayer in RCT+ was significantly greater than that in RCT–. The invasiveness of RCT+ and RCT– cells was stimulated by additional recombinant mouse IL-1α (rIL-1α) in a dose-dependent manner. Anti-mouse IL-1α monoclonal antibody (anti-IL-1α mAb) significantly inhibited the invasiveness of RCT+ and RCT– cells through the MLE monolayer. However, in RCT+ cells these effects were higher than in RCT– cells. In an attachment assay, the ability of RCT+ cells to attach to the MLE monolayer was significantly higher than that of RCT– cells. The attachment ability of RCT+ and RCT– cells to the MLE monolayer was significantly increased by the pretreatment with rIL-1α in a dose-dependent manner. In a retraction assay, conditioned medium of RCT+ stimulated the retraction of the MLE monolayer more markedly in comparison with conditioned medium of RCT–. The retraction of the MLE monolayer was stimulated by additional rIL-1α in a dose-dependent manner. The increased retraction of the MLE monolayer was closely associated with the enhancement in tumor cell invasiveness. These findings suggest that IL-1α derived from RCT+ and RCT– cells might contribute to the enhancement of tumor cell invasion by stimulating the attachment to the MLE monolayer and retraction of the MLE monolayer.