title: Enhancement of head and neck squamous cell carcinoma proliferation, invasion, and metastasis by tumor-associated fibroblasts in preclinical models.
abstract: BACKGROUND
  Head and neck squamous cell carcinoma (HNSCC) has had little improvement in mortality rates in decades. A clearer understanding of the HNSCC tumor microenvironment will aid in finding more effective targeted therapies for this disease. Tumor-associated fibroblasts (TAFs) are the largest stromal cellular components of the tumor microenvironment in HNSCC.
  
  
  METHODS
  We isolated TAFs from clinical HNSCC cases and propagated in vitro. The effects of TAF-secreted paracrine factors on in vitro HNSCC migration, invasion, and proliferation was assessed. The effect of TAFs on HNSCC growth and metastases was determined in an orthotopic floor-of-the-mouth tumor model.
  
  
  RESULTS
  TAF-conditioned media increased HNSCC cell migration, invasion, and proliferation. TAFs increased HNSCC tumor growth and metastases in vivo.
  
  
  CONCLUSIONS
  TAFs play a major role in increasing tumor growth and metastasis in HNSCC. Targeting the tumor stroma may be important to reduce the rate of HNSCC metastasis.
authors.affiliation: Department of Otolaryngology, University of Pittsburgh and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Sarah Elizabeth
authors.initials: SE
authors.lastname: Wheeler
authors.forename: Huifang
authors.initials: H
authors.lastname: Shi
authors.forename: Fangchen
authors.initials: F
authors.lastname: Lin
authors.forename: Sumana
authors.initials: S
authors.lastname: Dasari
authors.forename: Joseph
authors.initials: J
authors.lastname: Bednash
authors.forename: Stephen
authors.initials: S
authors.lastname: Thorne
authors.forename: Simon
authors.initials: S
authors.lastname: Watkins
authors.forename: Radhika
authors.initials: R
authors.lastname: Joshi
authors.forename: Sufi Mary
authors.initials: SM
authors.lastname: Thomas
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D017077:Culture Media, Conditioned; D005347:Fibroblasts / Q000502:physiology; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D019899:Paracrine Communication / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077195:Squamous Cell Carcinoma of Head and Neck; D017154:Stromal Cells / Q000473:pathology; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D000199:Actins; D017077:Culture Media, Conditioned
keywords: head and neck cancer; invasion; metastasis; tumor microenvironment; tumor-associated fibroblasts