Soluble Interleukin-13Rα2 Decoy Receptor Inhibits Hodgkin's Lymphoma Growth in Vitro and in Vivo

Young Trieu; Xiao Yan Wen; Brian F. Skinnider; Mark R. Bray; Zhihua Li; Jaime O. Claudio; Esther Masih-Khan; Yuan Xiao Zhu; Suzanne Trudel; J. Andrea McCart; Tak W. Mak; A. Keith Stewart

doi:10.1158/0008-5472.CAN-03-3764

Soluble Interleukin-13Rα2 Decoy Receptor Inhibits Hodgkin's Lymphoma Growth in Vitro and in Vivo

Young Trieu, Xiao Yan Wen, Brian F. Skinnider, Mark R. Bray, Zhihua Li, Jaime O. Claudio, Esther Masih-Khan, Yuan Xiao Zhu, Suzanne Trudel, J. Andrea McCart, Tak W. Mak, A. Keith Stewart

Hematology/Oncology

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

Abstract

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-13Rα2) via adenoviral-mediated gene transfer would inhibit IL-13-induced Reed-Sternberg cell proliferation. Western blot and ELISA analysis verified expression of sIL-13Rα2 in cell lysates and supernatants of AdsIL-13Rα2-transduced COS-7 cells. Treatment of two IL-13-responsive HL-derived cell lines, HDLM-2 and L-1236, with AdsIL-13Rα2-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-13Rα2 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-13Rα2 led to the regression or stabilization of established tumors and was associated with diminished STAT6 phosphorylation. Our data demonstrate that AdsIL-13Rα2 can suppress HL growth in vitro and in vivo.

Original language	English (US)
Pages (from-to)	3271-3275
Number of pages	5
Journal	Cancer research
Volume	64
Issue number	9
DOIs	https://doi.org/10.1158/0008-5472.CAN-03-3764
State	Published - May 1 2004

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1158/0008-5472.CAN-03-3764

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title = "Soluble Interleukin-13Rα2 Decoy Receptor Inhibits Hodgkin's Lymphoma Growth in Vitro and in Vivo",

abstract = "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-13Rα2) via adenoviral-mediated gene transfer would inhibit IL-13-induced Reed-Sternberg cell proliferation. Western blot and ELISA analysis verified expression of sIL-13Rα2 in cell lysates and supernatants of AdsIL-13Rα2-transduced COS-7 cells. Treatment of two IL-13-responsive HL-derived cell lines, HDLM-2 and L-1236, with AdsIL-13Rα2-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-13Rα2 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-13Rα2 led to the regression or stabilization of established tumors and was associated with diminished STAT6 phosphorylation. Our data demonstrate that AdsIL-13Rα2 can suppress HL growth in vitro and in vivo.",

author = "Young Trieu and Wen, {Xiao Yan} and Skinnider, {Brian F.} and Bray, {Mark R.} and Zhihua Li and Claudio, {Jaime O.} and Esther Masih-Khan and Zhu, {Yuan Xiao} and Suzanne Trudel and McCart, {J. Andrea} and Mak, {Tak W.} and Stewart, {A. Keith}",

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AU - Trieu, Young

AU - Wen, Xiao Yan

AU - Skinnider, Brian F.

AU - Bray, Mark R.

AU - Li, Zhihua

AU - Claudio, Jaime O.

AU - Masih-Khan, Esther

AU - Zhu, Yuan Xiao

AU - Trudel, Suzanne

AU - McCart, J. Andrea

AU - Mak, Tak W.

AU - Stewart, A. Keith

PY - 2004/5/1

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N2 - 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-13Rα2) via adenoviral-mediated gene transfer would inhibit IL-13-induced Reed-Sternberg cell proliferation. Western blot and ELISA analysis verified expression of sIL-13Rα2 in cell lysates and supernatants of AdsIL-13Rα2-transduced COS-7 cells. Treatment of two IL-13-responsive HL-derived cell lines, HDLM-2 and L-1236, with AdsIL-13Rα2-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-13Rα2 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-13Rα2 led to the regression or stabilization of established tumors and was associated with diminished STAT6 phosphorylation. Our data demonstrate that AdsIL-13Rα2 can suppress HL growth in vitro and in vivo.

AB - 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-13Rα2) via adenoviral-mediated gene transfer would inhibit IL-13-induced Reed-Sternberg cell proliferation. Western blot and ELISA analysis verified expression of sIL-13Rα2 in cell lysates and supernatants of AdsIL-13Rα2-transduced COS-7 cells. Treatment of two IL-13-responsive HL-derived cell lines, HDLM-2 and L-1236, with AdsIL-13Rα2-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-13Rα2 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-13Rα2 led to the regression or stabilization of established tumors and was associated with diminished STAT6 phosphorylation. Our data demonstrate that AdsIL-13Rα2 can suppress HL growth in vitro and in vivo.

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Soluble Interleukin-13Rα2 Decoy Receptor Inhibits Hodgkin's Lymphoma Growth in Vitro and in Vivo

Abstract

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