Degranulation of mast cells induced by gastric cancer-derived adrenomedullin prompts gastric cancer progression

被引:36
作者
Lv, Yi-pin [1 ]
Peng, Liu-sheng [1 ]
Wang, Qi-hong [1 ]
Chen, Na [1 ]
Teng, Yong-sheng [1 ]
Wang, Ting-ting [1 ]
Mao, Fang-yuan [1 ]
Zhang, Jin-yu [1 ]
Cheng, Ping [1 ]
Liu, Yu-gang [1 ]
Kong, Hui [1 ]
Wu, Xiao-long [1 ]
Hao, Chuan-jie [1 ]
Chen, Weisan [2 ]
Zhu, Jiang [3 ,4 ,5 ]
Han, Bin [6 ]
Ma, Qiang [6 ]
Li, Ke [7 ]
Zou, Quanming [1 ]
Zhuang, Yuan [1 ]
机构
[1] Third Mil Med Univ, Coll Pharm, Natl Engn Res Ctr Immunol Prod, Dept Microbiol & Biochem Pharm, Chongqing, Peoples R China
[2] La Trobe Univ, Sch Mol Sci, La Trobe Inst Mol Sci, Bundoora, Vic 3085, Australia
[3] Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing 400038, Peoples R China
[4] Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing 400038, Peoples R China
[5] Key Lab Tumor Immunopathol, Chongqing 400038, Peoples R China
[6] Affiliated Hosp, North Sichuan Med Coll, Dept Pharm, Nanchong, Sichuan, Peoples R China
[7] Chongqing Hosp Tradit Chinese Med, Dept Gen Surg, Chongqing, Peoples R China
来源
CELL DEATH & DISEASE | 2018年 / 9卷
基金
中国国家自然科学基金;
关键词
TUMOR; INFLAMMATION; ACTIVATION; EXPRESSION; NETWORKS; VESSELS; GROWTH; CD8(+); ROLES;
D O I
10.1038/s41419-018-1100-1
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Mast cells are prominent components of solid tumors and exhibit distinct phenotypes in different tumor microenvironments. However, their precise mechanism of communication in gastric cancer remains largely unclear. Here, we found that patients with GC showed a significantly higher mast cell infiltration in tumors. Mast cell levels increased with tumor progression and independently predicted reduced overall survival. Tumor-derived adrenomedullin (ADM) induced mast cell degranulation via PI3K-AKT signaling pathway, which effectively promoted the proliferation and inhibited the apoptosis of GC cells in vitro and contributed to the growth and progression of GC tumors in vivo, and the effect could be reversed by blocking interleukin (IL)-17A production from these mast cells. Our results illuminate a novel protumorigenic role and associated mechanism of mast cells in GC, and also provide functional evidence for these mast cells to prevent, and to treat this immunopathogenesis feature of GC.
引用
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页数:12
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