title: Chemotherapeutic alteration of VEGF, PDGF and PDGFRα/β expression under 5-FU vs. docetaxel in HPV-transformed squamous cell carcinoma compared to HPV-negative HNSCC in vitro.
abstract: BACKGROUND
  Head and neck squamous cell carcinoma (HNSCC) is the most common malignant epithelial tumor in the upper aerodigestive tract. The incidence of HNSCC induced by the oncogenic human papilloma virus (HPV) is rising, indicating a growing importance of the viral etiology. Cell proliferation, migration and tumor vascularization are regulated by a set of angiogenic peptides such as PDGF (platelet-derived growth factor), PDGFRα/β (platelet-derived growth factor receptor α/β) and VEGF (vascular endothelial growth factor). In locally advanced HNSCC docetaxel is used for induction chemotherapy (ICT) combined with platinum-based chemotherapy and 5-fluorouracil (5-FU). This study sought to evaluate the expression of angiogenic factors (VEGF, PDGF and PDGFRα/β) in HPV-positive (CERV196) and HPV-negative squamous cell carcinoma (HNSCC 11A and 14C) and the efficacy of chemotherapy with docetaxel as a potential treatment modality, compared to 5-FU as a single-drug application.
  
  
  METHODS
  Tumor cell lines were incubated with 5-FU or docetaxel at a concentration of 1.0 and 5.0 μmol/ml. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical analyses were carried out after 48, 72, 120, 192 and 240 hours, in order to identify changes in protein expression of VEGF, PDGF and PDGFRα/β.
  
  
  RESULTS
  We demonstrated a significant reduction of VEGF and PDGFRβ expression after incubation with docetaxel by ELISA and of PDGF by immunohistochemistry, irrespective of the HPV status, whereas the application of 5-FU had a significantly weaker impact on the expression of angiogenic peptides. HPV-positive CERV196 cells were characterized by a reduced susceptibility to a docetaxel-altered expression.
  
  
  CONCLUSIONS
  Although neither of the applied drugs are selective anti-angiogenic agents, docetaxel surprisingly was demonstrated to cause a significant decrease of angiogenic factors in this study.
authors: Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. christoph.aderhold@umm.de
authors: Christoph
authors: C
authors: Aderhold
authors: Claudia
authors: C
authors: Umbreit
authors: Anne
authors: A
authors: Faber
authors: Alexander
authors: A
authors: Sauter
authors: Jörg Ulrich
authors: JU
authors: Sommer
authors: Richard
authors: R
authors: Birk
authors: Philipp
authors: P
authors: Erben
authors: Ralf-Dieter
authors: RD
authors: Hofheinz
authors: Jens
authors: J
authors: Stern-Straeter
authors: Karl
authors: K
authors: Hörmann
authors: Johannes David
authors: JD
authors: Schultz
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D049109:Cell Proliferation / Q000187:drug effects; D002472:Cell Transformation, Viral / Q000187:drug effects*; D000077143:Docetaxel; D004797:Enzyme-Linked Immunosorbent Assay; D005472:Fluorouracil / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D052162:Human papillomavirus 16 / Q000472:pathogenicity*; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D030361:Papillomavirus Infections / Q000188:drug therapy / Q000378:metabolism / Q000821:virology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010982:Platelet-Derived Growth Factor; D043823:Taxoids; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C075278:platelet-derived growth factor A; D000077143:Docetaxel; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D005472:Fluorouracil
keywords: PDGFRα/β; Vascular endothelial growth factor; docetaxel; fluorouracil; head and neck squamous cell carcinoma; platelet-derived growth factor