title: Expression and functional activity of heat shock proteins in human glioblastoma multiforme.
abstract: OBJECTIVE
  To assess the expression of heat shock proteins (HSP) in glioma cells in vitro and in vivo and to examine their role in resistance to apoptosis.
  
  
  BACKGROUND
  HSP are expressed in response to various forms of stress. Constitutive HSP expression may confer resistance to cytotoxic stimuli in human cancers.
  
  
  METHODS
  HSP expression was assessed by immunoblot analysis in glioma cells in vitro and by immunocytochemistry in human glioblastomas in vivo. Modulation of apoptosis by hyperthermia-mediated HSP induction was examined in glioma cell lines in vitro.
  
  
  RESULTS
  Immunoblot analysis revealed constitutive expression of HSP27, HSP72, HSP73, and HSP90 in all 12 human glioma cell lines. B-crystallin (alphaBC) was expressed in 3 of 12 cell lines. High levels of alphaBC and HSP72 correlated with drug resistance and high p53 levels in vitro. Transient hyperthermia (43 degrees C/2 hours) induced HSP27 and HSP72 expression but had no effect on the levels of alphaBC, HSP73, or HSP90. HSP induction provided no survival advantage against subsequent cytotoxic challenges, including cytotoxic cytokines and radiochemotherapy. Immunohistochemistry showed strong expression of all HSP in vivo. The comparative analysis of HSP27, alphaBC, HSP72, HSP73, and HSP90 expression in 24 paired samples of first resections and recurrences of human glioblastoma multiforme revealed no impact of HSP expression on response to adjuvant radiochemotherapy and no modulation of HSP expression by radiochemotherapy.
  
  
  CONCLUSIONS
  High constitutive, as opposed to inducible, expression of HSP may play a role in the primary resistance of human malignant gliomas to cytotoxic radiochemotherapy. Superinduction of HSP levels by hyperthermia in vitro provided no further survival advantage.
authors.affiliation: Department of Neurology, University of Tübingen School of Medicine, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hermisson
authors.forename: H
authors.initials: H
authors.lastname: Strik
authors.forename: J
authors.initials: J
authors.lastname: Rieger
authors.forename: J
authors.initials: J
authors.lastname: Dichgans
authors.forename: R
authors.initials: R
authors.lastname: Meyermann
authors.forename: M
authors.initials: M
authors.lastname: Weller
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D013997:Time Factors
chemical_list: D006360:Heat-Shock Proteins