title: Selective inhibition of matrix metalloproteinase-14 blocks tumor growth, invasion, and angiogenesis.
abstract: Inhibition of specific matrix metalloproteinases (MMP) 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.
authors.affiliation: Dyax Corp, Cambridge, Massachusetts 02139, USA. ldevy@dyax.com
authors.forename: Laetitia
authors.initials: L
authors.lastname: Devy
authors.forename: Lili
authors.initials: L
authors.lastname: Huang
authors.forename: Laurent
authors.initials: L
authors.lastname: Naa
authors.forename: Niranjan
authors.initials: N
authors.lastname: Yanamandra
authors.forename: Henk
authors.initials: H
authors.lastname: Pieters
authors.forename: Nicolas
authors.initials: N
authors.lastname: Frans
authors.forename: Edward
authors.initials: E
authors.lastname: Chang
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Tao
authors.forename: Marc
authors.initials: M
authors.lastname: Vanhove
authors.forename: Annabelle
authors.initials: A
authors.lastname: Lejeune
authors.forename: Reinoud
authors.initials: R
authors.lastname: van Gool
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sexton
authors.forename: Guannan
authors.initials: G
authors.lastname: Kuang
authors.forename: Douglas
authors.initials: D
authors.lastname: Rank
authors.forename: Shannon
authors.initials: S
authors.lastname: Hogan
authors.forename: Csaba
authors.initials: C
authors.lastname: Pazmany
authors.forename: Yu Lu
authors.initials: YL
authors.lastname: Ma
authors.forename: Sonia
authors.initials: S
authors.lastname: Schoonbroodt
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Nixon
authors.forename: Robert C
authors.initials: RC
authors.lastname: Ladner
authors.forename: Rene
authors.initials: R
authors.lastname: Hoet
authors.forename: Paula
authors.initials: P
authors.lastname: Henderikx
authors.forename: Chris
authors.initials: C
authors.lastname: Tenhoor
authors.forename: Shafaat A
authors.initials: SA
authors.lastname: Rabbani
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Valentino
authors.forename: Clive R
authors.initials: CR
authors.lastname: Wood
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Dransfield
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D007150:Immunohistochemistry; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D009361:Neoplasm Invasiveness / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D014162:Transfection; D014183:Transplantation, Heterologous; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C000608273:DX-2400; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors