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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 expression of 950 genes in Hodgkin's disease (HD) by analyzing differential mRNA expression using microarrays. In two independent microarray experiments, the HD-derived cell lines L428 and KMH2 were compared with an Epstein-Barr virus (EBV)-immortalized lymphoblastoid B cell line, LCL-GK. Interleukin (IL)-13 and IL-5 were found to be highly expressed in the HD-derived cell lines. Examination of IL-13 and IL-5 expression by Northern blot analysis and enzyme-linked immunosorbent assay confirmed these results and revealed the expression of IL-13 in a third HD-derived cell line, HDLM2. Control LCL and EBV-negative non-Hodgkin lymphoma–derived cell lines did not express IL-13. In situ hybridization of lymph node tissue from HD patients showed that elevated levels of IL-13 were specifically expressed by Hodgkin/Reed-Sternberg (H/RS) tumor cells. Treatment of a HD-derived cell line with a neutralizing antibody to IL-13 resulted in a dose-dependent inhibition of H/RS cell proliferation. These data suggest that H/RS cells produce IL-13 and that IL-13 plays an important role in the stimulation of H/RS cell growth, possibly by an autocrine mechanism. Modulation of the IL-13 signaling pathway may be a logical objective for future therapeutic strategies.

Key Words: lymphoma • cytokines • cDNA microarray • gene expression • proliferation

U. Kapp's current address is University Medical Center, Department of Hematology/Oncology, Hugstetter Strasse 55, 79106 Freiburg, Germany.

Abbreviations used: HD, Hodgkin's disease; H/RS, Hodgkin/ Reed-Sternberg; NHL, non-Hodgkin lymphoma.

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