INTERLEUKIN-1-ALPHA ACTS AS AN AUTOCRINE GROWTH STIMULATOR FOR HUMAN GASTRIC-CARCINOMA CELLS

The expression and effect of interleukin 1alpha (IL-1alpha) were exami ned in human gastric carcinoma cell lines to determine if IL-1alpha ac ts as a growth stimulator for these cells. Six of 8 gastric carcinoma cell lines expressed IL-1alpha mRNA at various levels. Among them, TMK -1 and MKN-7 cells secreted IL-1alpha into the culture fluid, in an es pecially large amount by MKN-7 cells. Scatchard plot analysis of IL-1a lpha binding revealed that TMK-1 cells had only one type of high-affin ity receptors, whereas MKN-7 cells had high- and low-affinity receptor s. Cell growth and DNA synthesis of TMK-1 and MKN-7 cells were stimula ted by IL-1alpha, and those of MKN-7 were inhibited by addition of ant i-IL-1alpha antibody or IL-1 receptor antagonist. The expression of IL -1alpha mRNA by these cell lines was induced by either IL-1alpha, epid ermal growth factor, or transforming growth factor alpha. On the other hand, IL-1alpha increased the mRNA expression for transforming growth factor alpha and epidermal growth factor receptor. These findings ind icate that IL-1alpha is an autocrine growth stimulator for gastric car cinoma cells and the interaction with epidermal growth factor/transfor ming growth factor alpha/receptor system should be involved in the gro wth modulation by IL-1alpha.