In vivo overexpression of IL-13 receptor alpha2 chain inhibits tumorigenicity of human breast and pancreatic tumors in immunodeficient mice.
Interleukin 13 receptor alpha2 (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.
Kawakami
K
K
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Kawakami
M
M
Snoy
P J
PJ
Husain
S R
SR
Puri
R K
RK
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053661:Interleukin-13 Receptor alpha1 Subunit; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D018123:Receptors, Interleukin / Q000235:genetics* / Q000276:immunology; D053660:Receptors, Interleukin-13; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
C508181:IL13RA1 protein, human; C508183:Il13ra1 protein, mouse; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13