Selective Inhibition of Matrix Metalloproteinase-14 Blocks Tumor Growth, Invasion, and Angiogenesis

被引：276

作者：

Devy, Laetitia ^{[1
]}

Huang, Lili ^{[1
]}

Naa, Laurent ^{[2
]}

Yanamandra, Niranjan ^{[1
]}

Pieters, Henk ^{[2
]}

Frans, Nicolas ^{[2
]}

Chang, Edward ^{[1
]}

Tao, Qingfeng ^{[1
]}

Vanhove, Marc ^{[2
]}

Lejeune, Annabelle ^{[2
]}

van Gool, Reinoud ^{[2
]}

Sexton, Daniel J. ^{[1
]}

Kuang, Guannan ^{[1
]}

Rank, Douglas ^{[1
]}

Hogan, Shannon ^{[1
]}

Pazmany, Csaba ^{[1
]}

Ma, Yu Lu ^{[1
]}

Schoonbroodt, Sonia ^{[2
]}

Nixon, Andrew E. ^{[1
]}

Ladner, Robert C. ^{[1
]}

Hoet, Rene ^{[2
]}

Henderikx, Paula ^{[2
]}

TenHoor, Chris ^{[1
]}

Rabbani, Shafaat A. ^{[3
]}

Valentino, Maria Luisa ^{[3
]}

Wood, Clive R. ^{[1
]}

Dransfield, Daniel T. ^{[1
]}

机构：

[1] Dyax Corp, Cambridge, MA 02139 USA

[2] Dyax SA, Liege, Belgium

[3] McGill Univ, Dept Med, Ctr Hlth, Montreal, PQ, Canada

来源：

CANCER RESEARCH | 2009年 / 69卷 / 04期

关键词：

OVARIAN-CARCINOMA CELLS; BREAST-CANCER; MICE DEFICIENT; MT1-MMP; EXPRESSION; METASTASIS; ACTIVATION; GENERATION; ANTIBODIES; AFFINITY;

D O I：

10.1158/0008-5472.CAN-08-3255

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Inhibition of specific matrix metalloproteinases (MNIP) is an attractive noncytotoxic approach to cancer therapy. MMP-14, a membrane-bound zinc endopeptidase, has been proposed to play a central role in tumor growth, invasion, and neovascularization. Besides cleaving matrix proteins, MMP-14 activates proMMP-2 leading to an amplification of pericellular proteolytic activity. To examine the contribution of MMP-14 to tumor growth and angiogenesis, we used DX-2400, a highly selective fully human MMP-14 inhibitory antibody discovered using phage display technology. DX-2400 blocked proMMP-2 processing on tumor and endothelial cells, inhibited angiogenesis, and slowed tumor progression and formation of metastatic lesions. The combination of potency, selectivity, and robust in vivo activity shows the potential of a selective MMP-14 inhibitor for the treatment of solid tumors. [Cancer Res 2009;69(4):1517-26]

引用

页码：1517 / 1526

页数：10

共 40 条

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