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Clin Cancer Res. 2009 Jun 15;15(12):4058-65. doi: 10.1158/1078-0432.CCR-09-0212. Epub 2009 Jun 9.

Anti-EMMPRIN monoclonal antibody as a novel agent for therapy of head and neck cancer.

Author information

1
Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Abstract

PURPOSE:

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.

EXPERIMENTAL DESIGN:

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.

PMID:
19509148
PMCID:
PMC2796106
DOI:
10.1158/1078-0432.CCR-09-0212
[Indexed for MEDLINE]
Free PMC Article

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