title: Anti-EMMPRIN monoclonal antibody as a novel agent for therapy of head and neck cancer.
abstract: OBJECTIVE
  Extracellular matrix metalloprotease inducer (EMMPRIN) is a tumor surface protein that promotes growth and is overexpressed in head and neck cancer. These features make it a potential therapeutic target for monoclonal antibody (mAb)-based therapy. Because molecular therapy is considered more effective when delivered with conventional cytotoxic agents, anti-EMMPRIN therapy was assessed alone and in combination with external beam radiation.
  
  
  METHODS
  Using a murine flank model, loss of EMMPRIN function was achieved by transfection with a small interfering RNA against EMMPRIN or treatment with a chimeric anti-EMMPRIN blocking mAb. Cytokine expression was assessed for xenografts, tumor cells, fibroblasts, and endothelial cells.
  
  
  RESULTS
  Animals treated with anti-EMMPRIN mAb had delayed tumor growth compared with untreated controls, whereas treatment with combination radiation and anti-EMMPRIN mAb showed the greatest reduction in tumor growth (P = 0.001). Radiation-treated EMMPRIN knockdown xenografts showed a reduction in tumor growth compared with untreated knockdown controls (P = 0.01), whereas radiation-treated EMMPRIN-expressing xenografts did not show a delay in tumor growth. Immunohistochemical evaluation for Ki67 and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) resulted in a reduction in proliferation (P = 0.007) and increased apoptosis in anti-EMMPRIN mAb-treated xenografts compared with untreated controls (P = 0.087). In addition, we provide evidence that EMMPRIN suppression results in decreased interleukin 1beta (IL-1beta), IL-6, and IL-8 cytokine production, in vitro and in vivo.
  
  
  CONCLUSIONS
  These data suggest that anti-EMMPRIN antibody inhibits tumor cell proliferation in vivo and may represent a novel targeted treatment option in head and neck squamous cell carcinoma.
authors.affiliation: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Dean
authors.forename: J Robert
authors.initials: JR
authors.lastname: Newman
authors.forename: Emily E
authors.initials: EE
authors.lastname: Helman
authors.forename: Wenyue
authors.initials: W
authors.lastname: Zhang
authors.forename: Seena
authors.initials: S
authors.lastname: Safavy
authors.forename: D M
authors.initials: DM
authors.lastname: Weeks
authors.forename: Mark
authors.initials: M
authors.lastname: Cunningham
authors.forename: Linda A
authors.initials: LA
authors.lastname: Snyder
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.forename: Lacey R
authors.initials: LR
authors.lastname: McNally
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Buchsbaum
authors.forename: Eben L
authors.initials: EL
authors.lastname: Rosenthal
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D051926:Basigin / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D051379:Mice; D016513:Mice, SCID; D034741:RNA, Small Interfering / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; C497886:BSG protein, human; D016207:Cytokines; D007155:Immunologic Factors; D034741:RNA, Small Interfering; D051926:Basigin