M. Kornmann et al., Pancreatic cancer cells express interleukin-13 and -4 receptors, and theirgrowth is inhibited by Pseudomonas exotoxin coupled to interleukin-13 and -4, ANTICANC R, 19(1A), 1999, pp. 125-131
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.