Pancreatic cancer cells express interleukin-13 and -4 receptors, and their growth is inhibited by pseudomonas exotoxin coupled to interleukin-13 and -4

Marko Kornmann, JÖrg Kleeff, Waldemar Debinski, Murray Korc

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Background: Interleukin (IL)-13 and -4 are malfunctional 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 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 recepators and the common γ chain (γ(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-13Rα1 and IL-4Rα, one cell line expressed IL-13Rα2, and 5 pancreatic cancer cell lines expressed γ(c). IL-13 (5 nM) significantly enhanced ther 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 μg/ml for IL-13-PE38QQR and from 20 ng/ml to 10 μg/ml for IL-4-PE38QQR. IL-13 and -4 antagonized these inhibitory activities in some, but not all, of these 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 ultimateky have a role in the treatment of pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)125-131
Number of pages7
JournalAnticancer Research
Volume19
Issue number1 A
StatePublished - Apr 20 1999

Keywords

  • Human pancreatic cancer
  • IL-4/13-pseudomonas exotoxin chimeric protein
  • Interleukin-4/-13

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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