Pancreatic cancer cells express interleukin-13 and -4 receptors, and theirgrowth is inhibited by Pseudomonas exotoxin coupled to interleukin-13 and -4

Background: Interleukin (IL)-13 and -4 are multifunctional cytokines that b ind to specific cell-surface receptors. The aim of this study was to determ ine whether pancreatic cancer cells express either receptor, and to assess the growth suppressive effects of chimeric proteins composed of a Pseudomon as exotoxin (PE) A mutant (PE38QQR) fused to IL-13 (IL-13 PE38QQR) or IL-4 (IL-4-PE38QQR) in these cells. Materials and Methods: Northern and Western blot analysis were used to analyze the expression of IL-4/-13 receptors and the common gamma chain (gamma(c)) in pancreatic cancer cell lines. MTT gro wth assays were carried out to assess the effects of IL-4/-13 and IL-4/-13- PE38QQR on cell growth. Results: All 6 pancreatic cancer cell lines examine d expressed IL-13R alpha 1 and IL-4R alpha, one cell line expressed IL-13R alpha 5 and 5 pancreatic cancer cell lines expressed gamma(c). IL-13 (5 nM) significantly enhanced the growth of 3 cell lines, whereas IL-4 (5 nM) enh anced the growth of I cell line. In contrast, IL-13-PE38QQR and IL-4-PE38QQ R inhibited the growth of all 6 tested cell lines. There were large variati ons in the individual sensitivity of the cells, with LD50 values ranging fr om 100 ng/ml to 5 mu g/ml for IL-13-PE38QQR and from 20 ng/ml to 10 mu g/ml for IL-4-PE38QQR. IL-13 and -4 antagonized these inhibitory activities in some, bur not all, of the cell lines. Conclusions: IL-13 and -4 may act as mitogens toward pancreatic cancel cells by activating IL-4- and IL-IS-recep tors and IL-13- and IL-4-coupled toxins may ultimately have a role in the t reatment of pancreatic cancer.