期刊
CELLS
卷 10, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/cells10092485
关键词
glioblastoma; low-grade glioma; macrophages; retinoic acid; monocytic cells; single-cell sequencing; tumor microenvironment; tumor-associated macrophages; MMP; invasion; progression; enzyme
类别
资金
- Hearn Fund for Brain Tumor Research
- National Cancer Institute's Cancer Center Support Grant [P30CA012197]
The study indicates that high expression of ALDH1A2 in the GBM microenvironment, especially in M2 GAM, may promote the progression of GBM. The expression of ALDH1A2 is increased upon tumor recurrence and plays a crucial role in regulating the activity of macrophages.
Glioblastoma (GBM) is the most aggressive malignant glioma. Therapeutic targeting of GBM is made more difficult due to its heterogeneity, resistance to treatment, and diffuse infiltration into the brain parenchyma. Better understanding of the tumor microenvironment should aid in finding more effective management of GBM. GBM-associated macrophages (GAM) comprise up to 30% of the GBM microenvironment. Therefore, exploration of GAM activity/function and their specific markers are important for developing new therapeutic agents. In this study, we identified and evaluated the expression of ALDH1A2 in the GBM microenvironment, and especially in M2 GAM, though it is also expressed in reactive astrocytes and multinucleated tumor cells. We demonstrated that M2 GAM highly express ALDH1A2 when compared to other ALDH1 family proteins. Additionally, GBM samples showed higher expression of ALDH1A2 when compared to low-grade gliomas (LGG), and this expression was increased upon tumor recurrence both at the gene and protein levels. We demonstrated that the enzymatic product of ALDH1A2, retinoic acid (RA), modulated the expression and activity of MMP-2 and MMP-9 in macrophages, but not in GBM tumor cells. Thus, the expression of ALDH1A2 may promote the progressive phenotype of GBM.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据