Pancreatic cancer cells express interleukin-13 and -4 receptors, and their growth is inhibited by Pseudomonas exotoxin coupled to interleukin-13 and -4.
BACKGROUND
Interleukin (IL)-13 and -4 are multifunctional cytokines that bind to specific cell-surface receptors. The aim of this study was to determine whether pancreatic cancer cells express either receptor, and to assess the growth suppressive effects of chimeric proteins composed of a Pseudomonas exotoxin (PE) A mutant (PE38QQR) fused to IL-13 (IL-13-PE38QQR) or IL-4 (IL-4-PE38QQR) in these cells.


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 growth 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 examined expressed IL-13R alpha 1 and IL-4R alpha, one cell line expressed IL-13R alpha 2, 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) enhanced the growth of 1 cell line. In contrast, IL-13-PE38QQR and IL-4-PE38QQR inhibited the growth of all 6 tested cell lines. There were large variations in the individual sensitivity of the cells, with LD50 values ranging from 100 ng/ml to 5 micrograms/ml for IL-13-PE38QQR and from 20 ng/ml to 10 micrograms/ml for IL-4-PE38QQR. IL-13 and -4 antagonized these inhibitory activities in some, but not all, of the cell lines.


CONCLUSIONS
IL-13 and -4 may act as mitogens toward pancreatic cancer cells by activating IL-4- and IL-13-receptors and IL-13- and IL-4-coupled toxins may ultimately have a role in the treatment of pancreatic cancer.
Kornmann
M
M
Department of Medicine, University of California, Irvine 92697, USA. mkorc@uci.edu
Kleeff
J
J
Debinski
W
W
Korc
M
M
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D002455:Cell Division / Q000187:drug effects; D005098:Exotoxins / Q000494:pharmacology*; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018123:Receptors, Interleukin / Q000032:analysis*; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000032:analysis*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C508181:IL13RA1 protein, human