A Soluble Form of B Cell Maturation Antigen, a Receptor for the Tumor Necrosis Factor Family Member APRIL, Inhibits Tumor Cell Growth

doi:10.1084/jem.192.11.1677

Published online 4 December 2000.

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© The Rockefeller University Press, 0022-1007/2000/12/1677/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 11, December 4, 2000 1677-1684

Brief Definitive Report

A Soluble Form of B Cell Maturation Antigen, a Receptor for the Tumor Necrosis Factor Family Member APRIL, Inhibits Tumor Cell Growth

Paul Rennert^b, Pascal Schneider^a, Teresa G. Cachero^b, Jeffrey Thompson^b, Luciana Trabach^b, Sylvie Hertig^a, Nils Holler^a, Fang Qian^b, Colleen Mullen^b, Kathy Strauch^b, Jeffrey L. Browning^b, Christine Ambrose^b, and Jürg Tschopp^a
^a Institute of Biochemistry, BIL Biomedical Research Center, University of Lausanne, CH-1066 Epalinges, Switzerland
^b Departments of Molecular Genetics, Immunology, Inflammation, Cell Biology, and Protein Engineering, Biogen, Incorporated, Cambridge, Massachusetts 02142

Correspondence to: Jürg Tschopp, Institute of Biochemistry, University of Lausanne, Ch. des Boveresses 155, CH-1066 Epalinges, Switzerland. Tel:41-21-692-5738 Fax:41-21-692-5705 E-mail:jurg.tschopp{at}ib.unil.ch.

A proliferation-inducing ligand (APRIL) is a ligand of the tumornecrosis factor (TNF) family that stimulates tumor cell growthin vitro and in vivo. Expression of APRIL is highly upregulatedin many tumors including colon and prostate carcinomas. Herewe identify B cell maturation antigen (BCMA) and transmembraneactivator and calcium modulator and cyclophilin ligand (CAML)interactor (TACI), two predicted members of the TNF receptorfamily, as receptors for APRIL. APRIL binds BCMA with higheraffinity than TACI. A soluble form of BCMA, which inhibits theproliferative activity of APRIL in vitro, decreases tumor cellproliferation in nude mice. Growth of HT29 colon carcinoma cellsis blocked when mice are treated once per week with the solublereceptor. These results suggest an important role for APRILin tumorigenesis and point towards a novel anticancer strategy.

Key Words: tumor necrosis factor, tumorigenesis, cell survival, apoptosis,cancer therapy

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