title: Fibroblast growth factor receptors are components of autocrine signaling networks in head and neck squamous cell carcinoma cells.
abstract: OBJECTIVE
  We previously reported that a fibroblast growth factor (FGF) receptor (FGFR) signaling pathway drives growth of lung cancer cell lines of squamous and large cell histologies. Herein, we explored FGFR dependency in cell lines derived from the tobacco-related malignancy, head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  FGF and FGFR mRNA and protein expression was assessed in nine HNSCC cell lines. Dependence on secreted FGF2 for cell growth was tested with FP-1039, an FGFR1-Fc fusion protein. FGFR and epidermal growth factor receptor (EGFR) dependence was defined by sensitivity to multiple inhibitors selective for FGFRs or EGFR.
  
  
  RESULTS
  FGF2 was expressed in eight of the nine HNSCC cell lines examined. Also, FGFR2 and FGFR3 were frequently expressed, whereas only two lines expressed FGFR1. FP-1039 inhibited growth of HNSCC cell lines expressing FGF2, identifying FGF2 as an autocrine growth factor. FGFR inhibitors selectively reduced in vitro growth and extracellular signal-regulated kinase signaling in three HNSCC cell lines, whereas three distinct lines exhibited responsiveness to both EGFR and FGFR inhibitors. Combinations of these drugs yielded additive growth inhibition. Finally, three cell lines were highly sensitive to EGFR tyrosine kinase inhibitors (TKI) with no contribution from FGFR pathways.
  
  
  CONCLUSIONS
  FGFR signaling was dominant or codominant with EGFR in six HNSCC lines, whereas three lines exhibited little or no role for FGFRs and were highly EGFR dependent. Thus, the HNSCC cell lines can be divided into subsets defined by sensitivity to EGFR and FGFR-specific TKIs. FGFR inhibitors may represent novel therapeutics to deploy alone or in combination with EGFR inhibitors in HNSCC.
authors.affiliation: Departments of Craniofacial Biology and Radiation Oncology, University of Colorado Denver Anschutz Medical Campus, Aurora, CO80045, USA.
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Marshall
authors.forename: Trista K
authors.initials: TK
authors.lastname: Hinz
authors.forename: Scott A
authors.initials: SA
authors.lastname: Kono
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Singleton
authors.forename: Brady
authors.initials: B
authors.lastname: Bichon
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Ware
authors.forename: Lindsay
authors.initials: L
authors.lastname: Marek
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Frederick
authors.forename: David
authors.initials: D
authors.lastname: Raben
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Heasley
mesh_terms: D019898:Autocrine Communication; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases