D-Mannose Slows Glioma Growth by Modulating Myeloperoxidase Activity

Abstract

Host immune response in the tumor microenvironment plays key roles in tumorigenesis. We hypothesized that D-mannose, a simple sugar with anti-inflammatory properties, could decrease oxidative stress and slow glioma progression. Using a glioma stem cell model in immunocompetent mice, we induced gliomas in the brain and tracked MPO activity in vivo with and without D-mannose treatment. As expected, we found that D-mannose treatment decreased the number of MPO+ cells and slowed glioma progression compared to PBS-treated control animals with gliomas. Unexpectedly, instead of decreasing MPO activity, D-mannose increased MPO activity in vivo, revealing that D-mannose boosted the MPO activity per MPO+ cell. On the other hand, D-glucose had no effect on MPO activity. To better understand this effect, we examined the effect of D-mannose on bone marrow-derived myeloid cells. We found that D-mannose modulated MPO activity via two mechanisms: directly via N-glycosylation of MPO, which boosted the MPO activity of each molecule, and indirectly by increasing H2O2 production, the main substrate for MPO. This increased host immune response acted to reduce tumor size, suggesting that increasing MPO activity such as through D-mannose administration may be a potential new therapeutic direction for glioma treatment.

Machine learning-based identification of glycosyltransferase-related mRNAs for improving outcomes and the anti-tumor therapeutic response of gliomas

“…The positive correlation between glycosyltransferase and tumor immunity has been recognized (Dusoswa et al, 2020;Jalali Motlagh et al, 2021). Glycosyltransferase alterations could change the nature of the TME and reverse adverse characteristics of TME cells, altering a "cold tumor" into a "hot tumor."…”

“…The positive correlation between glycosyltransferase and tumor immunity has been recognized ( Dusoswa et al, 2020 ; Jalali Motlagh et al, 2021 ). Glycosyltransferase alterations could change the nature of the TME and reverse adverse characteristics of TME cells, altering a “cold tumor” into a “hot tumor.” For example, the changed glycosyltransferase motifs on Mucin 1 (MUC1) could promote cancer immune surveillance by interacting with CD169, which enhances macrophage activation after binding to sialylated MUC1 and promotes tumor growth ( Reily et al, 2019 ).…”