Glycogen metabolism in an oral dysplastic/cancerous (iodine-negative) epithelium: Glycogen was consumed in the pentose phosphate pathway, not in glycolysis

Publication date: Available online 17 January 2019

Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology

Author(s): Nobuhiko Yoshimura, Shin-ichi Yamada, Hitoshi Aizawa, Tiepeng Xiao, Fumihiro Nishimaki, Hiroshi Kurita

Abstract

The purpose of this study was to investigate differences in glycogen metabolism (glycogen synthesis and glycolysis) between dysplastic/malignant (iodine-negative) and normal (iodine-positive) oral epithelial tissue. Twenty-two frozen samples of iodine-positive and -negative mucosal tissue were obtained from 22 oral squamous cell carcinoma (OSCC) patients. Serial frozen sections were cut and analyzed using hematoxylin-eosin and periodic acid-Schiff methods and immunohistochemical (IHC) staining for glucokinase (GK), phosphoglucomutase 3 (PGM3), and glucose-6-phosphatase (G6 Pase) to investigate glycogen metabolism. The expression levels of metabolites in OSCC and normal oral epithelial tissue were subjected to a metabolome analysis to clarify differences in central carbon metabolism, including glycogen metabolism. No significant differences were observed in GK or PGM3 immunoactivity between iodine-positive and -negative areas. However, G6 Pase immunoreactivity was significantly stronger in the upper layers of the negative epithelium. In the metabolome analysis, significant differences were noted in the last half of glycolysis. Lactic acid as the final metabolite in glycolysis was detected in the dysplastic/cancerous oral epithelium, and its levels were slightly higher than those in the normal epithelium. G6 Pase expression was significantly strong in dysplastic/cancerous oral epithelial cells. Dysplastic/cancerous oral epithelial cells exhibited stronger activation for glucose metabolism. The results of the metabolome analysis suggest that glucose and glycogen degradation products in oral dysplastic/cancerous epithelial cells are used for nucleic acid synthesis through the pentose phosphate pathway.

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