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

Journal of Neuro-oncology
Andrea O FontanaMichael Reinert

Abstract

The extent of 5-aminolevulinic acid (5-ALA) guided tumor resection has a determining impact in high-grade glioma and glioblastoma surgery. Yet the intensity of the 5-ALA induced fluorescence may vary within the tumor. We aimed to correlate 5-ALA induced fluorescence with the expression of epithelial growth factor receptor (EGFR) and its constitutively active version EGFRvIII in different glioblastoma (GBM) cell lines. To elucidate the role of EGFR in the metabolism of 5-ALA in GBM cell lines with variable EGFR expression status, 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 (siRNA) on HO-1 enzyme were analyzed in respect to 5-ALA induced fluorescence. Furthermore, inhibition of EGFR by Gefitinib was tested. A significant difference in 5-ALA induced fluorescence was obtained in U87MG (low EGFR expression) and LN229EGFR cells (EGFR overexpression) compared to BS153 (EGFR overexpression/EGFRvIII+). Treatment of U87MG and LN229EGFR cells wit...Continue Reading

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Citations

Aug 6, 2019·Frontiers in Surgery·Michael ReinertMaria Luisa D'Angelo
Sep 15, 2020·Chinese Neurosurgical Journal·Lianwang LiTao Jiang
Nov 18, 2019·Journal of Photochemistry and Photobiology. B, Biology·Deborah PiffarettiMaria Luisa D'Angelo
Mar 13, 2020·Journal of Photochemistry and Photobiology. B, Biology·Deborah PiffarettiMaria Luisa D'Angelo
Mar 9, 2021·World Neurosurgery·Nicholas B DadarioRandy S D'Amico

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Methods Mentioned

BETA
FACS
flow cytometry
PCR
transfection
surgical tumor resection

Software Mentioned

Elements AR
Prism
NIS
Kaluza

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