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In Vivo Overexpression of IL-13 Receptor α2 Chain Inhibits Tumorigenicity of Human Breast and Pancreatic Tumors in Immunodeficient Mice

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-13...

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Autores principales: Kawakami, Koji, Kawakami, Mariko, Snoy, Philip J., Husain, Syed R., Puri, Raj K.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193574/
https://www.ncbi.nlm.nih.gov/pubmed/11748276
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author Kawakami, Koji
Kawakami, Mariko
Snoy, Philip J.
Husain, Syed R.
Puri, Raj K.
author_facet Kawakami, Koji
Kawakami, Mariko
Snoy, Philip J.
Husain, Syed R.
Puri, Raj K.
author_sort Kawakami, Koji
collection PubMed
description 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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spelling pubmed-21935742008-04-14 In Vivo Overexpression of IL-13 Receptor α2 Chain Inhibits Tumorigenicity of Human Breast and Pancreatic Tumors in Immunodeficient Mice Kawakami, Koji Kawakami, Mariko Snoy, Philip J. Husain, Syed R. Puri, Raj K. J Exp Med Original Article 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. The Rockefeller University Press 2001-12-17 /pmc/articles/PMC2193574/ /pubmed/11748276 Text en Copyright © 2001, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Kawakami, Koji
Kawakami, Mariko
Snoy, Philip J.
Husain, Syed R.
Puri, Raj K.
In Vivo Overexpression of IL-13 Receptor α2 Chain Inhibits Tumorigenicity of Human Breast and Pancreatic Tumors in Immunodeficient Mice
title In Vivo Overexpression of IL-13 Receptor α2 Chain Inhibits Tumorigenicity of Human Breast and Pancreatic Tumors in Immunodeficient Mice
title_full In Vivo Overexpression of IL-13 Receptor α2 Chain Inhibits Tumorigenicity of Human Breast and Pancreatic Tumors in Immunodeficient Mice
title_fullStr In Vivo Overexpression of IL-13 Receptor α2 Chain Inhibits Tumorigenicity of Human Breast and Pancreatic Tumors in Immunodeficient Mice
title_full_unstemmed In Vivo Overexpression of IL-13 Receptor α2 Chain Inhibits Tumorigenicity of Human Breast and Pancreatic Tumors in Immunodeficient Mice
title_short In Vivo Overexpression of IL-13 Receptor α2 Chain Inhibits Tumorigenicity of Human Breast and Pancreatic Tumors in Immunodeficient Mice
title_sort in vivo overexpression of il-13 receptor α2 chain inhibits tumorigenicity of human breast and pancreatic tumors in immunodeficient mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193574/
https://www.ncbi.nlm.nih.gov/pubmed/11748276
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