This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Trieu, Y. Articles by Stewart, A. K. Search for Related Content PubMed PubMed Citation Articles by Trieu, Y. Articles by Stewart, A. K.

Soluble Interleukin-13R2 Decoy Receptor Inhibits Hodgkin’s Lymphoma Growth in Vitro and in Vivo

¹ Division of Experimental Therapeutics, Toronto General Research Institute, McLaughlin Centre for Molecular Medicine, and ² Advanced Medical Discovery Institute, Departments of Immunology and Medical Biophysics, University Health Network, University of Toronto, Toronto, Ontario, Canada

Recent studies have demonstrated that the malignant Reed-Sternberg cells of Hodgkin’s lymphoma (HL) secrete and are responsive to interleukin (IL)-13. We hypothesized that overexpression of a soluble IL-13 decoy receptor (sIL-13R2) via adenoviral-mediated gene transfer would inhibit IL-13-induced Reed-Sternberg cell proliferation. Western blot and ELISA analysis verified expression of sIL-13R2 in cell lysates and supernatants of AdsIL-13R2-transduced COS-7 cells. Treatment of two IL-13-responsive HL-derived cell lines, HDLM-2 and L-1236, with AdsIL-13R2-conditioned medium, resulted in the inhibition of cell proliferation, and down-regulated the phosphorylation of signal transducer and activator of transcription 6 (STAT6), an important mediator of IL-13 signaling. i.v. delivery of AdsIL-13R2 in NOD/SCID mice with s.c. implanted HDLM-2 cells delayed tumor onset and growth while enhancing survival compared with control mice. Intratumoral administration of AdsIL-13R2 led to the regression or stabilization of established tumors and was associated with diminished STAT6 phosphorylation. Our data demonstrate that AdsIL-13R2 can suppress HL growth in vitro and in vivo.

This article has been cited by other articles:

				O. Ritz, C. Guiter, F. Castellano, K. Dorsch, J. Melzner, J.-P. Jais, G. Dubois, P. Gaulard, P. Moller, and K. Leroy Recurrent mutations of the STAT6 DNA binding domain in primary mediastinal B-cell lymphoma Blood, August 6, 2009; 114(6): 1236 - 1242. [Abstract] [Full Text] [PDF]

				C. Aspord, A. Pedroza-Gonzalez, M. Gallegos, S. Tindle, E. C. Burton, D. Su, F. Marches, J. Banchereau, and A. K. Palucka Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T cells that facilitate tumor development J. Exp. Med., May 14, 2007; 204(5): 1037 - 1047. [Abstract] [Full Text] [PDF]

				K. Kawakami, M. Terabe, M. Kawakami, J. A. Berzofsky, and R. K. Puri Characterization of a Novel Human Tumor Antigen Interleukin-13 Receptor {alpha}2 Chain. Cancer Res., April 15, 2006; 66(8): 4434 - 4442. [Abstract] [Full Text] [PDF]

				D. Re, R. Kuppers, and V. Diehl Molecular Pathogenesis of Hodgkin's Lymphoma J. Clin. Oncol., September 10, 2005; 23(26): 6379 - 6386. [Abstract] [Full Text] [PDF]

				M. Kawakami, K. Kawakami, M. Kioi, P. Leland, and R. K. Puri Hodgkin lymphoma therapy with interleukin-4 receptor-directed cytotoxin in an infiltrating animal model Blood, May 1, 2005; 105(9): 3707 - 3713. [Abstract] [Full Text] [PDF]