Glutaminase 2 expression is associated with regional heterogeneity of 5-aminolevulinic acid fluorescence in glioblastoma.

Abstract:

:Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is now a widely-used modality for glioblastoma (GBM) treatment. However, intratumoral heterogeneity of fluorescence intensity may reflect different onco-metabolic programs. Here, we investigated the metabolic mechanism underlying the heterogeneity of 5-ALA fluorescence in GBM. Using an in-house developed fluorescence quantification system for tumor tissues, we collected 3 types of GBM tissues on the basis of their fluorescence intensity, which was characterized as strong, weak, and none. Expression profiling by RNA-sequencing revealed 77 genes with a proportional relationship and 509 genes with an inverse relationship between gene expression and fluorescence intensity. Functional analysis and in vitro experiments confirmed glutaminase 2 (GLS2) as a key gene associated with the fluorescence heterogeneity. Subsequent metabolite profiling discovered that insufficient NADPH due to GLS2 underexpression was responsible for the delayed metabolism of 5-ALA and accumulation of protoporphyrin IX (PpIX) in the high fluorescence area. The expression level of GLS2 and related NADPH production capacity is associated with the regional heterogeneity of 5-ALA fluorescence in GBM.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Kim S,Kim JE,Kim YH,Hwang T,Kim SK,Xu WJ,Shin JY,Kim JI,Choi H,Kim HC,Cho HR,Choi A,Chowdhury T,Seo Y,Dho YS,Kim JW,Kim DG,Park SH,Kim H,Choi SH,Park S,Lee SH,Park CK

doi

10.1038/s41598-017-12557-3

subject

Has Abstract

pub_date

2017-09-22 00:00:00

pages

12221

issue

1

issn

2045-2322

pii

10.1038/s41598-017-12557-3

journal_volume

7

pub_type

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