|
KMID : 0620920200520050013
|
|
Experimental & Molecular Medicine
2020 Volume.52 No. 5 p.13 ~ p.13
|
|
|
Amplification of transglutaminase 2 enhances tumor-promoting inflammation in gastric cancers
|
|
Cho Sung-Yup
Oh Yu-Mi
Jeong Eui-Man
Park Sang-Hui
Lee Da-Keun
Wang Xiaorui
Zeng Qiqi
Qin Hongyu
Hu Fang
Gong Hui
Liu Xi
Zhang Guanjun
Na Deuk-Chae
Lee Ji-Eun
Chae Jee-Soo
Suh Yun-Suhk
Kong Seong-Ho
Lee Hyuk-Joon
Kim Jong-Il
Park Han-Soo
Zhang Chengsheng
Yang Han-Kwang
Lee Charles
|
|
|
Abstract
|
|
|
|
Tumor-promoting inflammation is a hallmark of cancer and is highly associated with tumor progression, angiogenesis, and metastasis. Tumor-associated macrophages (TAMs) are major drivers of tumor-promoting inflammation, but due to the complexity of the tumor microenvironment, the detailed regulatory mechanisms are still under investigation. Here, we investigated a novel role for transglutaminase 2 (TGM2) in the development of tumor-promoting inflammation and recruitment of TAMs to gastric cancer (GC) tissues. When estimated by array comparative genomic hybridization and droplet digital PCR, the copy numbers of the TGM2 gene were amplified in 13.6% (14/103) of GC patients and positively associated with TGM2 expression. Gene set enrichment analysis of expression microarray data for GC samples with high or low TGM2 expression showed that increased TGM2 expression was associated with tumor-promoting inflammation in GC. In addition, the expression of TGM2 was correlated with the expression of markers for macrophages, neutrophils, blood vessels, and lymphatic vessels. Overexpression of TGM2 in GC cells augmented the IL-1β-induced secretion of macrophage-recruiting chemokines and NF-κB activation. TGM2 protein levels were associated with the expression levels of the macrophage marker CD163 in human GC tissue samples. Moreover, GC patients with high expression of TGM2 had a worse prognosis than those with low expression of TGM2. These results suggest TGM2 as a novel regulator of the tumor microenvironment of GC and provide a promising target for constraining tumor-promoting inflammation.
|
|
|
KEYWORD
|
|
|
Cancer genomics, Gastric cancer, Tumour immunology
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
    
|