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

J Exp Med. 2000 Dec 4;192(11):1677-84. doi: 10.1084/jem.192.11.1677.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adaptor Proteins, Signal Transducing*
  • Animals
  • B-Cell Activating Factor
  • B-Cell Maturation Antigen
  • B-Lymphocytes / physiology*
  • Carrier Proteins / metabolism
  • Cell Division
  • Cell Line, Transformed
  • Cell Transformation, Neoplastic*
  • HT29 Cells
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Nude
  • Neoplasms / therapy
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Solubility
  • Transmembrane Activator and CAML Interactor Protein
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • B-Cell Activating Factor
  • B-Cell Maturation Antigen
  • CAMLG protein, human
  • Caml protein, mouse
  • Carrier Proteins
  • Membrane Proteins
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins
  • TNFRSF13B protein, human
  • TNFRSF17 protein, human
  • TNFSF13 protein, human
  • TNFSF13B protein, human
  • Tnfrsf13b protein, mouse
  • Tnfrsf17 protein, mouse
  • Tnfsf13 protein, mouse
  • Tnfsf13b protein, mouse
  • Transmembrane Activator and CAML Interactor Protein
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • Tumor Necrosis Factor-alpha