title: An in vitro study showing the three-dimensional microenvironment influence over the behavior of head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  The Head and Neck Squamous Cell Carcinoma (HNSCC) ranks sixth worldwide. The mechanisms of growth, invasion and metastasis of this pathology are extensively studied and generally related to specific variations in signaling pathways like the PI3K-Akt; however most of these competent studies have been performed bidimensionally, which may hide important questions. This study sought to analyze the influence of the microenvironment upon the behavior of HNSCC.
  
  
  METHODS
  The status of pAkt, NF-κB and Cyclin D1 proteins was accessed through immunofluorescence and western blot methods in HNSCC cell lines originating from tongue, pharynx and metastatic lymph node when submitted to a three-dimensional culture model utilizing a matrix system. A bidimensional culture model (monolayer) was used as control.
  
  
  RESULTS
  The HNSCC cell lines cultured three-dimensionally exhibited a growth pattern characterized by small isolated islands, different from the control group. When the three-dimensional model was applied, two of the studied cell lines showed the same expression pattern as the bidimensional model regarding nuclear or cytoplasmatic localization, as well as reduction of all protein levels; however, the cell line originated from tongue, which specially has the epidermal growth factor receptor constitutively activated, demonstrated nuclear translocation of pAkt and also an increase in the levels of Cyclin D1.
  
  
  CONCLUSIONS
  The results suggest the influence of the microenvironment upon the behavior of HNSCC cells due to the changed expression of proteins related to tumor growth and cellular invasion. Furthermore, intrinsically genetic conditions also played important roles over the cells, despite the culture model employed.
authors.affiliation: Department of Oral Pathology, School of Dentistry, University of São Paulo, São Paulo, SP, Brazil. fernandagiudice@usp.br
authors.forename: Fernanda
authors.initials: F
authors.lastname: Salgueiredo-Giudice
authors.forename: Aline
authors.initials: A
authors.lastname: Corrêa-Abrahão
authors.forename: Felipe
authors.initials: F
authors.lastname: Fornias-Sperandio
authors.forename: Aluana-Maria
authors.initials: AM
authors.lastname: da-Costa-Dal-Vechio
authors.forename: Décio
authors.initials: D
authors.lastname: dos-Santos-Pinto-Junior
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D019938:Cyclin D1 / Q000096:biosynthesis; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016328:NF-kappa B / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D000077195:Squamous Cell Carcinoma of Head and Neck; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment
chemical_list: D016328:NF-kappa B; D019938:Cyclin D1; D051057:Proto-Oncogene Proteins c-akt