title: Effects of bevacizumab on autocrine VEGF stimulation in bladder cancer cell lines.
abstract: BACKGROUND
  A functional vascular endothelial growth factor A (VEGF-A) autocrine loop is crucial for bladder cancer cell survival. We reasoned that treatment with the anti-VEGF antibody bevacizumab may result either in cell growth prevention or in the cell adaptation to compensate VEGF deprivation.
  
  
  METHODS
  The cytotoxicity of different levels of bevacizumab and its effect on the gene expression was analyzed in human bladder cancer cell lines.
  
  
  RESULTS
  Inhibition of bladder cancer cell proliferation was observed at >2.5 mg/ml of bevacizumab. Non-muscle-invasive bladder cancer cells expressed high concentrations of VEGF-A, and were less susceptible to bevacizumab inhibition. At 0.5 mg/ml (FDA approved concentration) of bevacizumab, cells increase their expression of VEGF-A, VEGF-A receptors and related growth factors.
  
  
  CONCLUSIONS
  Bevacizumab cytotoxicity is only observed at high concentration, and it is inversely correlated with the basal VEGF-A expression of the bladder cancer cells. This is the first report showing that, at clinical bevacizumab concentrations, cancer cells compensate the VEGF-A blockade, by improving the expression of VEGF-A and related genes, highlighting the need to follow the patient's adaptation response to bevacizumab treatment.
authors.affiliation: CEDOC, Departamento de Imunologia, Faculdade de Ciências Médicas, FCM, Universidade Nova de Lisboa, Lisboa, Portugal. paula.videira@fcm.unl.pt
authors.forename: Paula A
authors.initials: PA
authors.lastname: Videira
authors.forename: A Rita
authors.initials: AR
authors.lastname: Piteira
authors.forename: M Guadalupe
authors.initials: MG
authors.lastname: Cabral
authors.forename: Catarina
authors.initials: C
authors.lastname: Martins
authors.forename: Manuela
authors.initials: M
authors.lastname: Correia
authors.forename: Paulo
authors.initials: P
authors.lastname: Severino
authors.forename: Helena
authors.initials: H
authors.lastname: Gouveia
authors.forename: Mylène
authors.initials: M
authors.lastname: Carrascal
authors.forename: Joana F
authors.initials: JF
authors.lastname: Almeida
authors.forename: Hélder
authors.initials: H
authors.lastname: Trindade
authors.forename: Lúcio Lara
authors.initials: LL
authors.lastname: Santos
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D019898:Autocrine Communication / Q000187:drug effects*; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab