Published online 4 December 2000.
© 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
A Soluble Form of B Cell Maturation Antigen, a Receptor for the Tumor Necrosis Factor Family Member April, Inhibits Tumor Cell Growth
Paul Rennertb,
Pascal Schneidera,
Teresa G. Cacherob,
Jeffrey Thompsonb,
Luciana Trabachb,
Sylvie Hertiga,
Nils Hollera,
Fang Qianb,
Colleen Mullenb,
Kathy Strauchb,
Jeffrey L. Browningb,
Christine Ambroseb, and
Jürg Tschoppa
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
Institute of Biochemistry, University of Lausanne, Ch. des Boveresses 155, CH-1066 Epalinges, Switzerland.41-21-692-570541-21-692-5738
jurg.tschopp{at}ib.unil.ch
A proliferation-inducing ligand (APRIL) is a ligand of the tumor necrosis factor (TNF) family that stimulates tumor cell growth in vitro and in vivo. Expression of APRIL is highly upregulated in many tumors including colon and prostate carcinomas. Here we identify B cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI), two predicted members of the TNF receptor family, as receptors for APRIL. APRIL binds BCMA with higher affinity than TACI. A soluble form of BCMA, which inhibits the proliferative activity of APRIL in vitro, decreases tumor cell proliferation in nude mice. Growth of HT29 colon carcinoma cells is blocked when mice are treated once per week with the soluble receptor. These results suggest an important role for APRIL in tumorigenesis and point towards a novel anticancer strategy.
Key Words: tumor necrosis factor tumorigenesis cell survival apoptosis cancer therapy
P. Rennert and P. Schneider contributed equally to this work.
© 2000 The Rockefeller University Press

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