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

Abstract：

: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.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Lv YP,Peng LS,Wang QH,Chen N,Teng YS,Wang TT,Mao FY,Zhang JY,Cheng P,Liu YG,Kong H,Wu XL,Hao CJ,Chen W,Zhu J,Han B,Ma Q,Li K,Zou Q,Zhuang Y

doi

10.1038/s41419-018-1100-1

subject

Has Abstract

pub_date

2018-10-10 00:00:00

pages

1034

issue

10

issn

2041-4889

pii

10.1038/s41419-018-1100-1

journal_volume

9

pub_type

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