The expression and effect of interleukin 1α (IL-1α) were examined in human gastric carcinoma cell lines to determine if IL-1α acts as a growth stimulator for these cells. Six of 8 gastric carcinoma cell lines expressed IL-1α mRNA at various levels. Among them, TMK-1 and MKN-7 cells secreted IL-1α into the culture fluid, in an especially large amount by MNK-7 cells. Scatchard plot analysis of IL-1α binding revealed that TMK-1 cells had only one type of high-affinity receptors, whereas MKN-7 cells had high- and low-affinity receptors. Cell growth and DNA synthesis of TMK-1 and MKN-7 cells were stimulated by IL-1α, and those of MKN-7 were inhibited by addition of anti-IL-1α antibody or IL-1 receptor antagonist. The expression of IL-1α mRNA by these cell lines was induced by either IL-1α, epidermal growth factor, or transforming growth factor α. On the other hand, IL-1α increased the mRNA expression for transforming growth factor α and epidermal growth factor receptor. These findings indicate that IL-1α is an autocrine growth stimulator for gastric carcinoma cells and the interaction with epidermal growth factor/transforming growth factor α/receptor system should be involved in the growth modulation by IL-1α.
This work was supported in part by a Grant-in-Aid for a Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health and Welfare of Japan, a Grant-in-Aid from the Ministry of Education, Science, and Culture of Japan.