科研之友
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摘要
The high rate of glucose uptake to fuel the bioenergetic and anabolic demands of proliferating cancer cells is well recognized and is exploited with F-18-2-fluoro-2-deoxy-D-glucose positron emission tomography (F-18-FDG-PET) to image tumors clinically. In contrast, enhanced glucose storage as glycogen (glycogenesis) in cancer is less well understood and the availability of a noninvasive method to image glycogen in vivo could provide important biologic insights. Here, we demonstrate that F-18-N-(methyl-(2-fluoroethyl)-1H-[1,2,3] triazole-4-yl) glucosamine (F-18-NFTG) annotates glycogenesis in cancer cells and tumors in vivo, measured by PET. Specificity of glycogen labeling was demonstrated by isolating F-18-NFTG-associated glycogen and with stable knockdown of glycogen synthase 1, which inhibited F-18-NFTG uptake, whereas oncogene (Rab25) activation-associated glycogen synthesis led to increased uptake. We further show that the rate of glycogenesis is cell-cycle regulated, enhanced during the nonproliferative state of cancer cells. We demonstrate that glycogen levels, F-18-NFTG, but not F-18-FDG uptake, increase proportionally with cell density and G(1)-G(0) arrest, with potential application in the assessment of activation of oncogenic pathways related to glycogenesis and the detection of posttreatment tumor quiescence.
- 出版日期2014-3-1
