Interleukin 13 Is Secreted by and Stimulates the Growth of Hodgkin and Reed-Sternberg Cells

doi:10.1084/jem.189.12.1939

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J. Exp. Med., Volume 189, Number 12, June 21, 1999 1939-1946

Interleukin 13 Is Secreted by and Stimulates the Growth of Hodgkin and Reed-Sternberg Cells

By Ursula Kapp,^* Wen-Chen Yeh,^* Bruce Patterson, Andrew J. Elia,^* David Kägi,^* Alexandra Ho,^* Andrew Hessel,^* Mike Tipsword,^§ Alexia Williams,^§ Christine Mirtsos,^* Annick Itie,^* Matthew Moyle,^§ and Tak W. Mak^*

From the ^* Amgen Institute, Ontario Cancer Institute, the Department of Medical Biophysics, and the Department of Immunology, University of Toronto, Toronto, Ontario M5G 2C1, Canada; the Ontario Cancer Institute, Department of Oncologic Pathology, Toronto, Ontario M5G 2M9, Canada; and ^§ Amgen, Biosystems Analysis, Thousand Oaks, California 91320

Gene expression patterns can provide vital clues to the pathogenesis of neoplastic diseases. We investigated the expressionof 950 genes in Hodgkin's disease (HD) by analyzing differentialmRNA expression using microarrays. In two independent microarrayexperiments, the HD-derived cell lines L428 and KMH2 were comparedwith an Epstein-Barr virus (EBV)-immortalized lymphoblastoid Bcell line, LCL-GK. Interleukin (IL)-13 and IL-5 were found tobe highly expressed in the HD-derived cell lines. Examinationof IL-13 and IL-5 expression by Northern blot analysis and enzyme-linkedimmunosorbent assay confirmed these results and revealed the expressionof IL-13 in a third HD-derived cell line, HDLM2. Control LCL andEBV-negative non-Hodgkin lymphoma-derived cell lines did not expressIL-13. In situ hybridization of lymph node tissue from HD patientsshowed that elevated levels of IL-13 were specifically expressedby Hodgkin/Reed-Sternberg (H/RS) tumor cells. Treatment of a HD-derivedcell line with a neutralizing antibody to IL-13 resulted in adose-dependent inhibition of H/RS cell proliferation. These datasuggest that H/RS cells produce IL-13 and that IL-13 plays animportant role in the stimulation of H/RS cell growth, possiblyby an autocrine mechanism. Modulation of the IL-13 signaling pathwaymay be a logical objective for future therapeuticstrategies.

Key words: lymphoma; cytokines; cDNA microarray; gene expression; proliferation

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