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P08.50 Epithelial growth factor receptor expression influences 5-ALA glioblastoma induced fluorescence

2017; Oxford University Press; Volume: 19; Issue: suppl_3 Linguagem: Inglês

10.1093/neuonc/nox036.239

1523-5866

Michael Reinert, Deborah Piffaretti, Francesco Marchi, Floriana Burgio, Ana Bela Faia-Torres, Paolo Paganetti, Uwe Pieles, A. Fontana,

Photodynamic Therapy Research Studies

BACKGROUND: The extent of 5-aminolevulinic acid (5-ALA) guided tumor resection has a determining impact in glioma surgery. Although the intensity of the 5-ALA induced fluorescence has been described to vary in confirmed glioma, the detection method is currently subjective and non-quantitative. We correlated 5-ALA induced fluorescence with the quantitative expression of Epithelial Growth Factor Receptor (EGFR) in different glioblastoma (GBM) cell lines. METHODS: To elucidate the role of EGFR in the metabolism of 5-ALA in (U87MG and BS153), we analyzed the activation of EGFR by its primary ligand EGF, and its downstream effect on Heme oxygenase-1 (HO-1), a key enzyme regulating the metabolism of Protoporphyrin IX (PpIX), the fluorescent metabolite of 5-ALA. Effects of direct pharmacological inhibition by Tin(IV)-Protoporphyrin (SnPP) or gene knockdown by small interfering RNA on HO-1 enzyme were analyzed in respect to 5-ALA induced fluorescence. Results: A significant difference in 5-ALA induced fluorescence was obtained in U87MG compared to BS153 cell lines, correlating with the different quantitative EGFR expression. Treatment of U87MG cells with EGF was able to promote HO-1 transcription and expression in a concentration-dependent manner, leading to a reduced cellular fluorescence. This effect could be reversed by EGFR-specific siRNA treatment. Reducing HO-1 activity by SnPP or HO-1-specific siRNA significantly enhanced fluorescence, independently of EGFR quantitative expression. CONCLUSION: EGF-induced HO-1 protein expression was identified as a negative regulator of 5-ALA induced fluorescence, thus dependent of EGFR expression. These findings justify the clinical observation of different intensities of 5-ALA induced fluorescence in glioblastoma surgery.