Glycolytic metabolism and differentiation remodeling of hematopoietic stem cells in lung cancer

Abstract: Objective Lung cancer may be accompanied by the abnormal activity of hematopoietic stem cells (HSCs), which rapidly proliferate and are biased toward myeloid differentiation, leading to abnormal immune cell development and consequently tumor immune disorders. However, the mechanism underlying the altered behavioral function of HSCs in the tumor state remains unclear. Methods Meanwhile, glucose metabolism, which plays an important role in the self-renewal and differentiation of HSCs, is remodeled in lung carcinogenesis. The goal of this study was to examine the relationship between glucose metabolism and the abnormal activity of HSCs in a tumor environment. A LLC mouse model of lung cancer was established. Metabolomics assays were used to analyze the differences of metabolites and the metabolic pathways between HSCs of normal (N-HSCs) and tumor-bearing mice (T-HSCs). Results Pyruvate metabolic changes were observed the most. T-HSCs exhibited up-regulated oxidative phosphorylation, elevated mitochondrial number and activity, ATP and ROS levels. Injection of the gluconeogenesis inhibitor 2-DG into tumor-bearing mice resulted in altered proliferation and apoptosis of HSCs, reduced differentiation of myeloid cells, and decreased the myeloid-derived suppressor cells. Conclusions The present results suggest that glucose metabolic state in HSCs is altered during tumorigenesis. Glucose metabolism remodeling in tumor HSCs could change their differentiation preferences.