Glucose-6-phosphatase Expression–Mediated [18F]FDG Efflux in Murine Inflammation and Cancer Models View Full Text


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Article Info

DATE

2019-02-04

AUTHORS

Mi Jeong Kim, Chul-Hee Lee, Youngeun Lee, Hyewon Youn, Keon Wook Kang, JoonHo Kwon, Abass Alavi, Sean Carlin, Gi Jeong Cheon, June-Key Chung

ABSTRACT

Purpose2-Deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) accumulation in inflammatory lesions can confound the diagnosis of cancer. In this study, we investigated [18F]FDG accumulation and efflux in relation to the genes and proteins involved in glucose metabolism in murine inflammation and cancer models.Procedures[18F]FDG accumulation and [18F]FDG efflux were measured in cancer cells (breast cancer, glioma, thyroid cancer, and hepatoma cells) and RAW 264.7 cells (macrophages) activated with lipopolysaccharide (LPS). The levels of mRNA expression were measured by real-time quantitative PCR (qPCR). The expression of glucose metabolism–related proteins was detected by western blotting. Dynamic [18F]FDG positron emission tomography-computed tomography (PET/CT) images were acquired for 2 h in tumor-bearing BALB/c nude mice and inflammatory mice induced by turpentine oil.Results[18F]FDG accumulation in MDA-MB-231 (breast cancer) increased with time, but that of HepG2 (hepatoma) reached a constant level after 120 min. [18F]FDG efflux in HepG2 was faster than that in MDA-MB-231. HepG2 strongly expressed glucose-6-phosphatase (G6Pase) compared with MDA-MB-231. [18F]FDG accumulation increased with time, and [18F]FDG efflux accelerated after the activation of RAW 264.7 cells. The expression levels of G6Pase, glucose transporter1 and glucose transporter3 (GLUT1 and GLUT3), and hexokinase II (HK II) increased after the activation of RAW 264.7 cells. [18F]FDG efflux in activated macrophages was faster than that in MDA-MB-231 cancer cells. MDA-MB-231 strongly expressed HK II protein compared with the activated RAW 264.7. In murine models, [18F]FDG accumulation in MDA-MB-231 cancer and inflammatory lesions increased with time, but that in HepG2 tumor increased until 20–30 min (SUVmeans ± SD (tumor/muscle), 3.0 ± 1.3) and then decreased (2.1 ± 0.9 at 110–120 min).ConclusionsThere was no difference in the pattern of [18F]FDG accumulation with time in MDA-MB-231 tumors and inflammatory lesions. We found that [18F]FDG efflux accelerated in activated macrophages reflecting increased G6Pase expression after activation and lower expression of HK II protein than that in MDA-MB-231 cancer cells. More... »

PAGES

917-925

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11307-019-01316-7

DOI

http://dx.doi.org/10.1007/s11307-019-01316-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111908424

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30719695


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29 schema:description Purpose2-Deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) accumulation in inflammatory lesions can confound the diagnosis of cancer. In this study, we investigated [18F]FDG accumulation and efflux in relation to the genes and proteins involved in glucose metabolism in murine inflammation and cancer models.Procedures[18F]FDG accumulation and [18F]FDG efflux were measured in cancer cells (breast cancer, glioma, thyroid cancer, and hepatoma cells) and RAW 264.7 cells (macrophages) activated with lipopolysaccharide (LPS). The levels of mRNA expression were measured by real-time quantitative PCR (qPCR). The expression of glucose metabolism–related proteins was detected by western blotting. Dynamic [18F]FDG positron emission tomography-computed tomography (PET/CT) images were acquired for 2 h in tumor-bearing BALB/c nude mice and inflammatory mice induced by turpentine oil.Results[18F]FDG accumulation in MDA-MB-231 (breast cancer) increased with time, but that of HepG2 (hepatoma) reached a constant level after 120 min. [18F]FDG efflux in HepG2 was faster than that in MDA-MB-231. HepG2 strongly expressed glucose-6-phosphatase (G6Pase) compared with MDA-MB-231. [18F]FDG accumulation increased with time, and [18F]FDG efflux accelerated after the activation of RAW 264.7 cells. The expression levels of G6Pase, glucose transporter1 and glucose transporter3 (GLUT1 and GLUT3), and hexokinase II (HK II) increased after the activation of RAW 264.7 cells. [18F]FDG efflux in activated macrophages was faster than that in MDA-MB-231 cancer cells. MDA-MB-231 strongly expressed HK II protein compared with the activated RAW 264.7. In murine models, [18F]FDG accumulation in MDA-MB-231 cancer and inflammatory lesions increased with time, but that in HepG2 tumor increased until 20–30 min (SUVmeans ± SD (tumor/muscle), 3.0 ± 1.3) and then decreased (2.1 ± 0.9 at 110–120 min).ConclusionsThere was no difference in the pattern of [18F]FDG accumulation with time in MDA-MB-231 tumors and inflammatory lesions. We found that [18F]FDG efflux accelerated in activated macrophages reflecting increased G6Pase expression after activation and lower expression of HK II protein than that in MDA-MB-231 cancer cells.
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36 ConclusionsThere
37 D-glucose accumulation
38 G6Pase
39 G6Pase expression
40 HepG2
41 HepG2 tumors
42 MDA-MB-231
43 MDA-MB-231 cancer
44 MDA-MB-231 cancer cells
45 MDA-MB-231 tumors
46 PCR
47 Purpose2-Deoxy-2
48 RAW 264.7
49 RAW 264.7 cells
50 Western blotting
51 accumulation
52 activation
53 blotting
54 cancer
55 cancer cells
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57 cells
58 constant level
59 diagnosis
60 diagnosis of cancer
61 differences
62 efflux
63 expression
64 expression levels
65 genes
66 glucose metabolism
67 glucose metabolism-related proteins
68 glucose transporter1
69 images
70 inflammation
71 inflammatory lesions
72 inflammatory mice
73 lesions
74 levels
75 lipopolysaccharide
76 low expression
77 mRNA expression
78 macrophages
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81 mice
82 min
83 model
84 murine inflammation
85 murine model
86 nude mice
87 oil
88 patterns
89 positron emission tomography-computed tomography (PET-CT) images
90 protein
91 quantitative PCR
92 real-time quantitative PCR
93 relation
94 study
95 time
96 tomography images
97 transporter1
98 tumor-bearing BALB/c nude mice
99 tumors
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