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Sci Rep. 2019 Feb 26;9(1):2794. doi: 10.1038/s41598-019-38973-1.

G6Pase location in the endoplasmic reticulum: Implications on compartmental analysis of FDG uptake in cancer cells.

Author information

1
Department of Mathematics (DIMA), University of Genoa, Genoa, Italy. scussolini@dima.unige.it.
2
Nuclear Medicine Unit, Department of Health Science, University of Genova, Genoa, Italy.
3
Nuclear Medicine Unit, Policlinico San Martino Hospital, Genoa, Italy.
4
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
5
Unit of Cellular Biology, Policlinico San Martino Hospital, Genova, Italy.
6
Department of Pharmacy, Biochemistry Laboratory, University of Genova, Genova, Italy.
7
Department of Mathematics (DIMA), University of Genoa, Genoa, Italy.
8
CNR Institute SPIN, Genoa, Italy.
9
CNR Institute of Bioimages and Molecular Physiology, Milan, Italy.

Abstract

The favourable kinetics of 18F-fluoro-2-deoxyglucose (FDG) permits to depict cancer glucose consumption by a single evaluation of late tracer uptake. This standard procedure relies on the slow radioactivity loss, usually attributed to the limited tumour expression of G6P-phosphatase (G6Pase). However, this classical interpretation intrinsically represents an approximation since, as in all tissues, cancer G6Pase activity is remarkable and is confined to the endoplasmic reticulum (ER), whose lumen must be reached by phosphorylated FDG to explain its hydrolysis and radioactivity release. The present study tested the impact of G6Pase sequestration on the mathematical description of FDG trafficking and handling in cultured cancer cells. Our data show that accounting for tracer access to the ER configures this compartment as the preferential site of FDG accumulation. This is confirmed by the reticular localization of fluorescent FDG analogues. Remarkably enough, reticular accumulation rate of FDG is dependent upon extracellular glucose availability, thus configuring the same ER as a significant determinant of cancer glucose metabolism.

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