Glioblastoma stem cell-specific histamine tumor microenvironment remodeling

被引：42

作者：

Chen, Jiayi ^{[1
]}

Liu, Guangqin ^{[1
,2
]}

Wang, Xinzheng ^{[1
]}

Hong, Hao ^{[1
]}

Li, Tingting ^{[1
]}

Li, Lin ^{[1
]}

Wang, Hongxiang ^{[3
]}

Xie, Jiong ^{[4
]}

Li, Bohan ^{[4
]}

Li, Ting ^{[1
]}

Lu, Dingyi ^{[1
]}

Zhang, Yakun ^{[1
]}

Zhao, Haixin ^{[1
,5
]}

Yao, Chengcheng ^{[1
]}

Wen, Kaiqing ^{[1
]}

Li, Teng ^{[1
]}

Chen, Jing ^{[1
]}

Wu, Shengming ^{[1
]}

He, Kun ^{[1
]}

Zhang, Wei-Na ^{[1
]}

Zhao, Jie ^{[1
]}

Wang, Na ^{[1
]}

Han, Qiuying ^{[1
]}

Xia, Qing ^{[1
]}

Qi, Ji ^{[4
]}

Chen, Juxiang ^{[3
]}

Zhou, Tao ^{[1
]}

Man, Jianghong ^{[1
]}

Zhang, Xue-Min ^{[1
,2
]}

Li, Ai-Ling ^{[1
,2
]}

Pan, Xin ^{[1
,2
]}

机构：

[1] Nanhu Lab, Natl Ctr Biomed Anal, 27 Tai Ping Rd, Beijing 100850, Peoples R China

[2] Fudan Univ, Sch Basic Med Sci, Shanghai 200032, Peoples R China

[3] Naval Med Univ, Changhai Hosp, Dept Neurosurg, 168 Changhai Rd, Shanghai 200433, Peoples R China

[4] Fengtai Hosp, 99 Fengtai South Rd, Beijing, Peoples R China

[5] Fifth Med Ctr Chinese PLA Gen Hosp, Inst Hematol, State Key Lab Expt Haematol, Beijing, Peoples R China

来源：

CELL STEM CELL | 2022年 / 29卷 / 11期

关键词：

ANGIOGENESIS; GROWTH; GLIOMA; DIFFERENTIATION; RECEPTORS; ALLERGIES; CHROMATIN; HISTORY;

D O I：

10.1016/j.stem.2022.09.009

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

The communication between glioblastoma stem cells (GSCs) and the surrounding microenvironment is a prominent feature accounting for the aggressive biology of glioblastoma multiforme (GBM). However, the mechanisms by which GSCs proactively drive interactions with microenvironment is not well understood. In this study, we interrogated metabolites that are preferentially secreted from GSCs and found that GSCs produce and secrete histamine to shape a pro-angiogenic tumor microenvironment. This histamine -produc-ing ability is attributed to H3K4me3 modification-activated histidine decarboxylase (HDC) transcription via MYC. Notably, HDC is highly expressed in GBM, which is associated with poor survival of these patients. GSC-secreted histamine activates endothelial cells by triggering a histamine H1 receptor (H1R)-Ca2+-NF-kB axis, thereby promoting angiogenesis and GBM progression. Importantly, pharmacological blockage of H1R using antihistamines impedes the growth of GBM xenografts in mice. Our findings establish that GSC-specific metabolite secretion remodels the tumor microenvironment and highlight histamine targeting as a potential strategy for GBM therapy.

引用

页码：1531 / +

页数：24

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