A soluble form of B cell maturation antigen, a receptor for the tumor necrosis factor family member APRIL, inhibits tumor cell growth

被引:212
作者
Rennert, P
Schneider, P
Cachero, TG
Thompson, J
Trabach, L
Hertig, S
Holler, N
Qian, F
Mullen, C
Strauch, K
Browning, JL
Ambrose, C
Tschopp, J
机构
[1] Univ Lausanne, Inst Biochem, BIL Biomed Res Ctr, CH-1066 Epalinges, Switzerland
[2] Biogen Inc, Dept Mol Genet, Cambridge, MA 02142 USA
[3] Biogen Inc, Dept Immunol, Cambridge, MA 02142 USA
[4] Biogen Inc, Dept Inflammat, Cambridge, MA 02142 USA
[5] Biogen Inc, Dept Cell Biol, Cambridge, MA 02142 USA
[6] Biogen Inc, Dept Prot Engn, Cambridge, MA 02142 USA
关键词
tumor necrosis factor; tumorigenesis; cell survival; apoptosis; cancer therapy;
D O I
10.1084/jem.192.11.1677
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 turner 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.
引用
收藏
页码:1677 / 1683
页数:7
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