title: Modulation of tumor cell growth in vivo by extracellular matrix metalloprotease inducer.
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.
  
  
  METHODS
  In vivo study using FaDu tumor xenografts.
  
  
  METHODS
  Academic research facility.
  
  
  METHODS
  Severe combined immunodeficiency (SCID) mice.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  This study suggests that anti-EMMPRIN-targeted therapy may prove to be a novel treatment option in HNSCC.
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Alabama at Birmingham, USA.
authors.forename: J Robert
authors.initials: JR
authors.lastname: Newman
authors.forename: Isaac A
authors.initials: IA
authors.lastname: Bohannon
authors.forename: Wenyue
authors.initials: W
authors.lastname: Zhang
authors.forename: Joni B
authors.initials: JB
authors.lastname: Skipper
authors.forename: William E
authors.initials: WE
authors.lastname: Grizzle
authors.forename: Eben L
authors.initials: EL
authors.lastname: Rosenthal
mesh_terms: D000818:Animals; D051926:Basigin / Q000235:genetics*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000235:genetics; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000235:genetics; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D010039:Otorhinolaryngologic Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology*; D034741:RNA, Small Interfering; D014162:Transfection; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: C497886:BSG protein, human; D019394:Ki-67 Antigen; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D051926:Basigin; D020780:Matrix Metalloproteinase 9