Inhibition of tumor growth by antibody to ADAMTS1 in mouse xenografts of breast cancer.
ABSTRACT 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.
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.
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.
ADAMTS1 could be a promising molecular target for immunotherapy of breast cancer.
SourceAvailable from: Izza de Arao Tan[Show abstract] [Hide abstract]
ABSTRACT: Since it was first characterized in 1997, the ADAMTS (A Disintegrin and Metalloprotease with ThromboSpondin motifs) metalloprotease family has been associated with many physiological and pathological conditions. Of the 19 proteases belonging to this family, considerable attention has been devoted to the role of its first member ADAMTS1 in cancer. Elevated ADAMTS1 promotes pro-tumorigenic changes such as increased tumor cell proliferation, inhibited apoptosis and altered vascularization. Importantly it facilitates significant peritumoral remodeling of the extracellular matrix environment to promote tumor progression and metastasis. However, discrepancy exists, as several studies also depict ADAMTS1 as a tumor suppressor. This article reviews the current understanding of ADAMTS1 regulation and the consequence of its dysregulation in primary cancer and ADAMTS1-mediated pathways of cancer progression and metastasis. © 2013 Wiley Periodicals, Inc.International Journal of Cancer 02/2013; 133(10). DOI:10.1002/ijc.28127 · 6.20 Impact Factor