Affiliation:
1. Guangxi Normal University
Abstract
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.
Publisher
Research Square Platform LLC
Reference55 articles.
1. Siegel RL, Miller KD, Jemal A. Cancer statistics. 2015. CA: a cancer journal for clinicians. 2015;65(1):5–29.
2. Systemic and targeted therapies for early-stage lung cancer;Byron E;Cancer control: journal of the Moffitt Cancer Center,2014
3. Beyond the standard of care: a review of novel immunotherapy trials for the treatment of lung cancer;Hall RD;Cancer control: journal of the Moffitt Cancer Center,2013
4. Myeloid-derived suppressor cells as regulators of the immune system;Gabrilovich DI;Nat Rev Immunol,2009
5. Immunosuppressive Role of Myeloid-Derived Suppressor Cells and Therapeutic Targeting in Lung Cancer;Ma J;J Immunol Res,2018