Work

Modulation of Tumor Cell Growth In Vivo by Extracellular Matrix Metalloprotease Inducer

Year: 2008

Type: article

Abstract: OBJECTIVE: To investigate if loss of extracellular matrix metalloprotease inducer (EMMPRIN) will inhibit the growth of head and neck squamous cell carcinoma (HNSCC) tumor cell lines in vivo. Tumor cell-derived EMMPRIN is highly overexpressed in HNSCC and is thought to be induced by surrounding fibroblasts to stimulate matrix metalloproteases, which modulate tumor cell invasion, growth, and angiogenesis. DESIGN: In vivo study using FaDu tumor xenografts. SETTING: Academic research facility. SUBJECTS: Severe combined immunodeficiency (SCID) mice. INTERVENTIONS: The HNSCC cell line FaDu was transfected with EMMPRIN (FaDu/E), control vector (FaDu), or plasmid-expressing small-interfering RNA against EMMPRIN (FaDu/siE). Tumor cells combined with fibroblast cells were xenografted onto the flank of SCID mice. Tumors were measured biweekly over 4 weeks, at which time the mice were killed, and tumor samples were analyzed for proliferation (Ki-67 immunohistochemical analysis), vascularization (factor VIII staining), and apoptosis (TUNEL [terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling] assay). MAIN OUTCOME MEASURE: Growth of head and neck cancer cell lines genetically engineered to express variable levels of EMMPRIN. RESULTS: Tumor growth positively correlated and animal survival negatively correlated with increasing EMMPRIN expression. FaDu/E tumor growth was significantly larger at 4 weeks compared with FaDu tumors (P = .006). Similarly, the control vector-transfected FaDu tumors were significantly larger than FaDu/siE (P < .001). Immunohistochemical analysis demonstrated increased Ki-67 in EMMPRIN-transfected cells, without a significant change in the rate of apoptosis between groups. Vascular density and tumor formation rate also increased significantly with EMMPRIN expression. CONCLUSION: This study suggests that anti-EMMPRIN-targeted therapy may prove to be a novel treatment option in HNSCC.

Source: Archives of Otolaryngology - Head and Neck Surgery

DOI: 10.1001/archotol.134.11.1218

Authors: J. Robert Newman, Isaac A. Bohannon, Wenyue Zhang, Joni B. Skipper, William E. Grizzle, Eben L. Rosenthal

Institutions: University of Alabama at Birmingham, UAB Medicine

Language: English

Topic: Protease and Inhibitor Mechanisms

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Cancer Institute