Effects of bevacizumab on autocrine VEGF stimulation in bladder cancer cell lines
Paula A Videira1, A Rita Piteira, M Guadalupe Cabral
1CEDOC, Departamento de Imunologia, Faculdade de Ciências Médicas, FCM, Universidade Nova de Lisboa, Lisboa, Portugal. paula.videira@fcm.unl.pt
Introduction:
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.
