TNF inhibitor suppresses bone metastasis in a breast cancer cell line

Biochem Biophys Res Commun. 2011 Apr 15;407(3):525-30. doi: 10.1016/j.bbrc.2011.03.051. Epub 2011 Mar 23.


In the evolution of cancer, tumor necrosis factor-alpha (TNF-α) plays a paradoxical role. High doses induce significant anticancer effects, but conversely, physiologic and pathologic levels of TNF-α may be involved in cancer promotion, tumor growth, and metastasis. Infliximab is a chimeric murine monoclonal antibody that binds with high affinity to soluble and membrane TNF-α and inhibits binding of TNF-α to its receptors. In the present study, we investigated the effect of infliximab, a TNF-α antagonist, on breast cancer aggressiveness and bone metastases. Infliximab greatly reduced cell motility and bone metastases in a metastatic breast cancer cell line, MDA-MB-231. The mechanism of bone metastasis inhibition involved decreased expression of CXC chemokine receptor 4 (CXCR4) and increased expression of decorin, which is the prototype of an expanding family of small leucine-rich proteoglycans. These results suggest a novel role for TNF-α inhibition in the reduction or prevention of bone metastases in this breast cancer model. Our study suggests that inhibition of TNF-α using infliximab may become a preventive therapeutic option for breast cancer.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / prevention & control*
  • Bone Neoplasms / secondary*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Female
  • Humans
  • Infliximab
  • Mice
  • Mice, Inbred BALB C
  • Radiography
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / biosynthesis
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Xenograft Model Antitumor Assays


  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • CXCR4 protein, human
  • Receptors, CXCR4
  • Tumor Necrosis Factor-alpha
  • Infliximab