Interleukin 13 receptor α2 (IL-13Rα2) chain is highly expressed on some tumor cell lines and primary cell cultures. This receptor chain plays an important role in ligand binding and internalization. To determine the functional significance of overexpression of this chain, we stably transfected IL-13Rα2 chain in human breast (MDA-MB-231) and pancreatic (PANC-1) cancer cell lines that naturally do not express this chain. There was no difference in growth between vector only transfected and IL-13Rα2 chain transfected cells in vitro. However, surprisingly, in immunodeficient mice, tumorigenicity was profoundly inhibited in IL-13Rα2 chain overexpressing tumors. Because breast tumors that grew later showed loss of IL-13Rα2 gene expression, lack of tumorigenicity correlated positively with IL-13Rα2 chain expression. Inflammatory cells including neutrophils and macrophages were identified in IL-13Rα2 overexpressing regressing tumors and neutrophils were found to produce IL-13. IL-13 showed a modest antitumor activity to IL-13Rα2 chain overexpressing tumors in vitro and in vivo. Furthermore, IL-13Rα2 chain overexpressing tumors constitutively produced IL-8 that has been shown to have antitumor effect. These results establish a novel function of a cytokine receptor chain and further suggest that the presence of this chain on tumor cells by itself may play a key role in tumorigenicity.
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17 December 2001
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December 17 2001
In Vivo Overexpression of IL-13 Receptor α2 Chain Inhibits Tumorigenicity of Human Breast and Pancreatic Tumors in Immunodeficient Mice
Koji Kawakami,
Koji Kawakami
1Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies
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Mariko Kawakami,
Mariko Kawakami
1Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies
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Philip J. Snoy,
Philip J. Snoy
2Division of Veterinary Services, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892
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Syed R. Husain,
Syed R. Husain
1Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies
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Raj K. Puri
Raj K. Puri
1Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies
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Koji Kawakami
1Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies
Mariko Kawakami
1Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies
Philip J. Snoy
2Division of Veterinary Services, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892
Syed R. Husain
1Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies
Raj K. Puri
1Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies
Address correspondence to Raj K. Puri, Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, NIH Bldg. 29B, Rm. 2NN10, 29 Lincoln Drive, MSC 4555, Bethesda, MD 20892. Phone: 301-827-0471; Fax: 301-827-0449; E-mail: [email protected]
*
Abbreviation used in this paper: PE, Pseudomonas exotoxin A.
Received:
March 01 2001
Revision Received:
October 17 2001
Accepted:
November 06 2001
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2001
J Exp Med (2001) 194 (12): 1743–1754.
Article history
Received:
March 01 2001
Revision Received:
October 17 2001
Accepted:
November 06 2001
Citation
Koji Kawakami, Mariko Kawakami, Philip J. Snoy, Syed R. Husain, Raj K. Puri; In Vivo Overexpression of IL-13 Receptor α2 Chain Inhibits Tumorigenicity of Human Breast and Pancreatic Tumors in Immunodeficient Mice . J Exp Med 17 December 2001; 194 (12): 1743–1754. doi: https://doi.org/10.1084/jem.194.12.1743
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