PMID- 10226533
OWN - NLM
STAT- MEDLINE
DCOM- 19990520
LR  - 20231213
IS  - 0250-7005 (Print)
IS  - 0250-7005 (Linking)
VI  - 19
IP  - 1A
DP  - 1999 Jan-Feb
TI  - Pancreatic cancer cells express interleukin-13 and -4 receptors, and their growth 
      is inhibited by Pseudomonas exotoxin coupled to interleukin-13 and -4.
PG  - 125-31
AB  - 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. 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 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.
FAU - Kornmann, M
AU  - Kornmann M
AD  - Department of Medicine, University of California, Irvine 92697, USA. 
      mkorc@uci.edu
FAU - Kleeff, J
AU  - Kleeff J
FAU - Debinski, W
AU  - Debinski W
FAU - Korc, M
AU  - Korc M
LA  - eng
GR  - CA-40162/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Bacterial Toxins)
RN  - 0 (Exotoxins)
RN  - 0 (IL13RA1 protein, human)
RN  - 0 (Interleukin-13)
RN  - 0 (Interleukin-13 Receptor alpha1 Subunit)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-13)
RN  - 0 (Receptors, Interleukin-4)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Virulence Factors)
RN  - 207137-56-2 (Interleukin-4)
RN  - EC 2.4.2.- (ADP Ribose Transferases)
SB  - IM
MH  - *ADP Ribose Transferases
MH  - *Bacterial Toxins
MH  - Cell Division/drug effects
MH  - Exotoxins/*pharmacology
MH  - Humans
MH  - Interleukin-13/*pharmacology
MH  - Interleukin-13 Receptor alpha1 Subunit
MH  - Interleukin-4/*pharmacology
MH  - Pancreatic Neoplasms/*drug therapy/pathology
MH  - Receptors, Interleukin/*analysis
MH  - Receptors, Interleukin-13
MH  - Receptors, Interleukin-4/*analysis
MH  - Recombinant Fusion Proteins/*pharmacology
MH  - Tumor Cells, Cultured
MH  - *Virulence Factors
MH  - Pseudomonas aeruginosa Exotoxin A
EDAT- 1999/05/05 00:00
MHDA- 1999/05/05 00:01
CRDT- 1999/05/05 00:00
PHST- 1999/05/05 00:00 [pubmed]
PHST- 1999/05/05 00:01 [medline]
PHST- 1999/05/05 00:00 [entrez]
PST - ppublish
SO  - Anticancer Res. 1999 Jan-Feb;19(1A):125-31.