A. Aggarwal1, Z. Yuan1, M. A. Nehs1 1Brigham And Women’s Hospital,Department Of Surgery,Boston, MA, USA
Introduction: Anaplastic thyroid cancer (ATC) is a fatal malignancy characterized by rapidly dividing tumor cells that demonstrate dependence on glycolysis for energy metabolism. We therefore sought to investigate the role of the glycolytic enzyme Hexokinase II (HK2) which is over expressed in many malignancies, including ATC. We hypothesized that a high glucose environment would promote HK2 gene expression and drive glycolytic energy capacity.
Methods: We cultured ATC cell lines (JL30 and 8505C) in high (25mM) or low (3mM) glucose concentrations for 96 hours. We analyzed HK2 expression by Fluorescent in-situ hybridization (FISH). We performed Seahorse XF Glycolytic stress tests to determine glycolytic reserve under each condition.
Results: We found higher and more variable HK2 expression in both ATC cell lines in the high glucose medium. JL30 had an average of 3.1 HK2 signals [Range 2-14] with high glucose environment versus 2.7 signals [Range 0-5] in the low glucose environment. Seahorse metabolic analysis revealed a glycolytic capacity of 245.8 mpH/min in the high glucose environment versus 55.9 mpH/min (p<0.001). 8505 had an average of 2.9 HK2 signals in the high glucose environment versus 2.7 in the low glucose environment. Seahorse metabolic analysis revealed a glycolytic capacity of 45.5 mpH/min for high glucose treatment versus 25.8 mpH in the low glucose treatment (p<0.01).
Conclusion: Here we demonstrate that a high glucose environment increases the expression of the glycolytic enzyme Hexokinase II and that this was associated with a higher metabolic glycolytic reserve. These studies are suggestive that the metabolism of anaplastic thyroid cancer cells is influenced by glucose concentrations. Future studies are needed to determine if hyperglycemia influences tumor biology in vivo.