Suppression of an IL-13 autocrine growth loop in a human Hodgkin/Reed-Sternberg tumor cell line by a novel IL-13 antagonist.
IL-13 has been proposed to be an autocrine growth factor for Hodgkin/Reed-Sternberg tumor cells (H/RS cells). Since we have recently identified and produced a novel IL-13 antagonist (IL-13E13K) that can suppress the biological activity of IL-13, here we examined whether IL-13E13K can inhibit growth of Hodgkin lymphoma (HL)-derived cell lines. IL-13E13K not only inhibited the growth of an unstimulated H/RS cell line (L1236) but also cells that were stimulated by exogenous IL-13 in a dose-dependent manner. Several HL-derived cell lines expressed IL-13 message and protein and message for various chains of IL-13R. H/RS cell lines expressed mRNA for the IL-13R alpha 1, IL-4R alpha, and IL-2R gamma chains. However, none of these cell lines expressed the IL-13R alpha 2 chain. An H/RS cell line (L1236) internalized the ligand-receptor complex after binding to a fusion protein composed of IL-13 and a mutated form of Pseudomonas exotoxin A (IL-13-PE38QQR, or IL-13 cytotoxin), as IL-13 cytotoxin was specifically cytotoxic to H/RS cells in vitro. These results indicate that IL-13E13K and IL-13 cytotoxin can effectively suppress growth of a L1236 H/RS cell line. Therefore, additional studies should be performed to determine the expression of IL-13 and IL-13R in primary clinical samples of Hodgkin's lymphoma and both agents should be further tested in vitro and in vivo as possible therapeutic agents for HL.
Oshima
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The Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, 29 Lincoln Drive, NIH Building 29B, Room 2NN10, Bethesda, Maryland 20892, USA.
Puri
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RK
D019898:Autocrine Communication; D002455:Cell Division; D004705:Endocytosis; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018793:Interleukin-13 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D053660:Receptors, Interleukin-13; D016539:Reed-Sternberg Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; C436826:interleukin 13 antagonist E13K