Dataset Information

Tumor-associated macrophage interleukin-? promotes glycerol-3-phosphate dehydrogenase activation, glycolysis and tumorigenesis in glioma cells.

ABSTRACT: Tumor-immune crosstalk within the tumor microenvironment (TME) occurs at all stages of tumorigenesis. Tumor-associated M2 macrophages play a central role in tumor development, but the molecular underpinnings have not been fully elucidated. We demonstrated that M2 macrophages produce interleukin 1? (IL-1?), which activates phosphorylation of the glycolytic enzyme glycerol-3-phosphate dehydrogenase (GPD2) at threonine 10 (GPD2 pT10) through phosphatidylinositol-3-kinase-mediated activation of protein kinase-delta (PKC?) in glioma cells. GPD2 pT10 enhanced its substrate affinity and increased the catalytic rate of glycolysis in glioma cells. Inhibiting PKC? or GPD2 pT10 in glioma cells or blocking IL-1? generated by macrophages attenuated the glycolytic rate and proliferation of glioma cells. Furthermore, human glioblastoma tumor GPD2 pT10 levels were positively correlated with tumor p-PKC? and IL-1? levels as well as intratumoral macrophage recruitment, tumor grade and human glioblastoma patient survival. These results reveal a novel tumorigenic role for M2 macrophages in the TME. In addition, these findings suggest possible treatment strategies for glioma patients through blockade of cytokine crosstalk between M2 macrophages and glioma cells.

SUBMITTER: Lu J

PROVIDER: S-EPMC7293068 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tumor-associated macrophage interleukin-β promotes glycerol-3-phosphate dehydrogenase activation, glycolysis and tumorigenesis in glioma cells.

Lu Jian J Xu Zhongye Z Duan Hubin H Ji Hongming H Zhen Zigang Z Li Bo B Wang Huangsuo H Tang Huoquan H Zhou Jie J Guo Tao T Wu Bin B Wang Dawei D Liu Yueting Y Niu Yuhu Y Zhang Ruisheng R

Cancer science 20200521 6

Tumor-immune crosstalk within the tumor microenvironment (TME) occurs at all stages of tumorigenesis. Tumor-associated M2 macrophages play a central role in tumor development, but the molecular underpinnings have not been fully elucidated. We demonstrated that M2 macrophages produce interleukin 1β (IL-1β), which activates phosphorylation of the glycolytic enzyme glycerol-3-phosphate dehydrogenase (GPD2) at threonine 10 (GPD2 pT10) through phosphatidylinositol-3-kinase-mediated activation of prot ...[more]

PMID: 32259365

Similar Datasets

Project description:Epidermal growth factor receptor (EGFR) signaling is a known mediator of colorectal carcinogenesis. Studies have focused on the role of EGFR signaling in epithelial cells, although the exact nature of the role of EGFR in colorectal carcinogenesis remains a topic of debate. Here, we present evidence that EGFR signaling in myeloid cells, specifically macrophages, is critical for colon tumorigenesis in the azoxymethane-dextran sodium sulfate (AOM-DSS) model of colitis-associated carcinogenesis (CAC). In a human tissue microarray, colonic macrophages demonstrated robust EGFR activation in the pre-cancerous stages of colitis and dysplasia. Utilizing the AOM-DSS model, mice with a myeloid-specific deletion of Egfr had significantly decreased tumor multiplicity and burden, protection from high-grade dysplasia and significantly reduced colitis. Intriguingly, mice with gastrointestinal epithelial cell-specific Egfr deletion demonstrated no differences in tumorigenesis in the AOM-DSS model. The alterations in tumorigenesis in myeloid-specific Egfr knockout mice were accompanied by decreased macrophage, neutrophil and T-cell infiltration. Pro-tumorigenic M2 macrophage activation was diminished in myeloid-specific Egfr-deficient mice, as marked by decreased Arg1 and Il10 mRNA expression and decreased interleukin (IL)-4, IL10 and IL-13 protein levels. Surprisingly, diminished M1 macrophage activation was also detectable, as marked by significantly reduced Nos2 and Il1b mRNA levels and decreased interferon (IFN)-?, tumor necrosis factor (TNF)-? and IL-1? protein levels. The alterations in M1 and M2 macrophage activation were confirmed in bone marrow-derived macrophages from mice with the myeloid-specific Egfr knockout. The combined effect of restrained M1 and M2 macrophage activation resulted in decreased production of pro-angiogenic factors, CXCL1 and vascular endothelial growth factor (VEGF), and reduced CD31+ blood vessels, which likely contributed to protection from tumorigenesis. These data reveal that EGFR signaling in macrophages, but not in colonic epithelial cells, has a significant role in CAC. EGFR signaling in macrophages may prove to be an effective biomarker of CAC or target for chemoprevention in patients with inflammatory bowel disease.

Dataset Information

Tumor-associated macrophage interleukin-? promotes glycerol-3-phosphate dehydrogenase activation, glycolysis and tumorigenesis in glioma cells.

Publications

Tumor-associated macrophage interleukin-β promotes glycerol-3-phosphate dehydrogenase activation, glycolysis and tumorigenesis in glioma cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets