The Journal of Experimental Medicine
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Published 17 December 2001. doi:10.1084/jem.194.12.1743
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© Rockefeller University Press, 0022-1007/2001/12/1743/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 12, December 17, 2001 1743-1754


Original Article

In Vivo Overexpression of IL-13 Receptor {alpha}2 Chain Inhibits Tumorigenicity of Human Breast and Pancreatic Tumors in Immunodeficient Mice

Koji Kawakami1, Mariko Kawakami1, Philip J. Snoy2, Syed R. Husain1 and Raj K. Puri1

1 Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies
2 Division of Veterinary Services, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892

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: puri{at}cber.fda.gov

Interleukin 13 receptor {alpha}2 (IL-13R{alpha}2) 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-13R{alpha}2 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-13R{alpha}2 chain transfected cells in vitro. However, surprisingly, in immunodeficient mice, tumorigenicity was profoundly inhibited in IL-13R{alpha}2 chain overexpressing tumors. Because breast tumors that grew later showed loss of IL-13R{alpha}2 gene expression, lack of tumorigenicity correlated positively with IL-13R{alpha}2 chain expression. Inflammatory cells including neutrophils and macrophages were identified in IL-13R{alpha}2 overexpressing regressing tumors and neutrophils were found to produce IL-13. IL-13 showed a modest antitumor activity to IL-13R{alpha}2 chain overexpressing tumors in vitro and in vivo. Furthermore, IL-13R{alpha}2 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.

Key Words: tumor antigen • neutrophil infiltration • tumorigenesis • IL-8 • cytokine receptor


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