Inhibition of tumor growth by antibody to ADAMTS1 in mouse xenografts of breast cancer

Anticancer Res. 2011 Nov;31(11):3839-42.

Abstract

Background: A disintegrin and metalloproteinase with thrombospondin motifs-1 (ADAMTS1), a member of the ADAMTS family of proteases, is involved in the shedding of epidermal growth factor (EGF)-like ligands such as amphiregulin, which activate the EGF receptor. Since ADAMTS1 has been implicated in aggressive breast carcinogenesis, we examined potential antitumor effects of antibody to ADAMTS1 in a mouse model of breast cancer.

Materials and methods: BALB/c female mice were inoculated with syngenic 4T1 breast cancer cells and treated with anti-ADAMTS1 antibody or control IgG. Tumor volume and weight were evaluated.

Results: Mouse 4T1 cells expressed ADAMTS1 and its substrates amphiregulin and heparin-binding EGF. Treatment with antibody to ADAMTS1 inhibited tumor growth without any adverse effects.

Conclusion: ADAMTS1 could be a promising molecular target for immunotherapy of breast cancer.

MeSH terms

  • ADAM Proteins / immunology*
  • ADAM Proteins / metabolism
  • ADAMTS1 Protein
  • Amphiregulin
  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Blotting, Northern
  • EGF Family of Proteins
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / immunology
  • ErbB Receptors / metabolism
  • Female
  • Glycoproteins / metabolism
  • Humans
  • Immunoblotting
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Mammary Neoplasms, Experimental / immunology*
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • AREG protein, human
  • Amphiregulin
  • Antibodies, Monoclonal
  • Areg protein, mouse
  • EGF Family of Proteins
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • ErbB Receptors
  • ADAM Proteins
  • ADAMTS1 Protein
  • Adamts1 protein, mouse