title: Inhibitory activity of bevacizumab to differentiation of retinoblastoma cells.
abstract: Vascular endothelial growth factor (VEGF) is a major regulator in retinal and choroidal angiogenesis, which are common causes of blindness in all age groups. Recently anti-VEGF treatment using anti-VEGF antibody has revolutionarily improved the visual outcome in patients with vaso-proliferative retinopathies. Herein, we demonstrated that bevacizumab as an anti-VEGF antibody could inhibit differentiation of retinoblastoma cells without affection to cellular viability, which would be mediated via blockade of extracellular signal-regulated kinase (ERK) 1/2 activation. The retinoblastoma cells expressed VEGFR-2 as well as TrkA which is a neurotrophin receptor associated with differentiation of retinoblastoma cells. TrkA in retinoblastoma cells was activated with VEGF treatment. Interestingly even in the concentration of no cellular death, bevascizumab significantly attenuated the neurite formation of differentiated retinoblastoma cells, which was accompanied by inhibition of neurofilament and shank2 expression. Furthermore, bevacizumab inhibited differentiation of retinoblastoma cells by blockade of ERK 1/2 activation. Therefore, based on that the differentiated retinoblastoma cells are mostly photoreceptors, our results suggest that anti-VEGF therapies would affect to the maintenance or function of photoreceptors in mature retina.
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Jang Won
authors.initials: JW
authors.lastname: Heo
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kim
authors.forename: Chang Sik
authors.initials: CS
authors.lastname: Cho
authors.forename: Hyoung Oh
authors.initials: HO
authors.lastname: Jun
authors.forename: Dong Hun
authors.initials: DH
authors.lastname: Kim
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Yu
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Kim
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D001483:Base Sequence; D000068258:Bevacizumab; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D012175:Retinoblastoma / Q000378:metabolism / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; C122162:SHANK2 protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D020917:Receptor, trkA; D040301:Vascular Endothelial Growth Factor Receptor-2; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3