title: αB-crystallin stimulates VEGF secretion and tumor cell migration and correlates with enhanced distant metastasis in head and neck squamous cell carcinoma.
abstract: BACKGROUND
  αB-crystallin is able to modulate vascular endothelial growth factor (VEGF) secretion. In many solid tumors VEGF is associated with angiogenesis, metastasis formation and poor prognosis. We set out to assess whether αB-crystallin expression is correlated with worse prognosis and whether this is related to VEGF secretion and cell motility in head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  αB-crystallin expression was determined immunohistochemically in tumor biopsies of 38 HNSCC patients. Locoregional control (LRC) and metastasis-free survival (MFS) of the patients were analyzed in relation to αB-crystallin expression. Additionally, the effects of αB-crystallin knockdown on VEGF secretion and cell motility were studied in vitro.
  
  
  RESULTS
  Patients with higher staining fractions of αB-crystallin exhibited a significantly shorter MFS (Log-Rank test, p < 0.005). Under normoxic conditions αB-crystallin knockdown with two different siRNAs in a HNSCC cell line reduced VEGF secretion 1.9-fold and 2.1-fold, respectively. Under hypoxic conditions, a similar reduction of VEGF secretion was observed, 1.9-fold and 2.2-fold, respectively. The effect on cell motility was assessed by a gap closure assay, which showed that αB-crystallin knockdown decreased the rate by which HNSCC cells were able to close a gap by 1.5- to 2.0-fold.
  
  
  CONCLUSIONS
  Our data suggest that αB-crystallin expression is associated with distant metastases formation in HNSCC patients. This association might relate to the chaperone function of αB-crystallin in mediating folding and secretion of VEGF and stimulating cell migration.
authors.affiliation: Department of Biomolecular Chemistry, Institute for Molecules and Materials and Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Chantal
authors.initials: C
authors.lastname: van de Schootbrugge
authors.forename: Johan
authors.initials: J
authors.lastname: Bussink
authors.forename: Paul N
authors.initials: PN
authors.lastname: Span
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.forename: Reidar
authors.initials: R
authors.lastname: Grénman
authors.forename: Hanneke
authors.initials: H
authors.lastname: Stegeman
authors.forename: Ger J M
authors.initials: GJ
authors.lastname: Pruijn
authors.forename: Johannes H A M
authors.initials: JH
authors.lastname: Kaanders
authors.forename: Wilbert C
authors.initials: WC
authors.lastname: Boelens
mesh_terms: D000704:Analysis of Variance; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015331:Cohort Studies; D003459:Crystallins / Q000378:metabolism / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D003459:Crystallins; D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A