Abstract 3733: Adenine nucleotide translocase2 mediates 18F-FDG uptake in dedifferentiated thyroid cancer

Abstract

Abstract Objectives: 18F-fluorodeoxyglucose (FDG), an analogue of glucose, provides valuable functional information based on the increased glucose uptake and glycolysis in malignant tumor cells. Although both glucose transporter-1 (GLUT-1) and hexokinase2 (HK2) activity have been considered to associate with FDG uptake, the molecular mechanisms that determine FDG uptake are still largely unknown. Adenine nucleotide translocase 2 (ANT2) in the mitochondria inner membrane was reported to relate with tumor malignancy. We investigated the correlation between FDG uptake and Glut-1, HK2, and ANT2 expression in thyroid cancers throughout various spectrums of differentiation status. Methods: N-thy-ori (normal human thyroid cells), WRO (follicular cancer), BHP10-3 and TPC-1 (papillary cancer), and FRO (anaplastic cancer) were used for this research. GLUT-1, HK2, and ANT2 expressions were measured by western blot. ANT2 siRNAs and pcDNA3.1-ANT2 vectors were used to modify ANT2 expression. FDG uptakes were measured in thyroid cells and human embryonic kidney cells (293FT) with HK2 or ANT2 transfection. For patient tissue analysis, 95 thyroid tissue-array cores were evaluated, and which are classified 36 as normal, 44 as poorly differentiated (PD), and 15 as anaplastic thyroid cancer (ATC). ANT2 expression was measured by immunostaining, scored from 1 to 5. Results: FDG uptake in thyroid cancer cells was increased in anaplastic and poorly differentiated cells (P<0.001). GLUT-1 expression was higher in both TPC-1 and FRO than other cells. Whereas, HK2 was expressed only in cancer cells. ANT2 was expressed only in FRO cells and the highest FDG accumulation was also observed in FRO. ANT2 siRNA showed decreased FDG uptake (0.55-fold) and ANT2 overexpression increased FDG uptake (1.7-fold). In 293FT cells, HK2 and ANT2 transfection increased FDG uptake (P<0.01). PD tissues (mean = 41.7, SD = 19.7) and ATC (mean = 48.0, SD = 25.6) tissues from patients showed higher ANT2 expression than normal (P<0.05). Conclusion: We showed that ANT2 was expressed only in anaplastic thyroid cancer cells, and this was related to FDG uptake. Higher level of ANT2 expression was observed in dedifferentiated cancer, and this indicates that ANT2 can be used as a marker of malignancy in thyroid cancer. Citation Format: Chul-Hee Lee, Hyewon Youn, Seock-Jin Chung, Ha Kim, Cho Rong Park, Mi Jeong Kim, Young Joo Park, Sun Wook Cho, Keon Wook Kang, June-Key Chung. Adenine nucleotide translocase2 mediates 18F-FDG uptake in dedifferentiated thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3733. doi:10.1158/1538-7445.AM2017-3733