Amplification of transglutaminase 2 enhances tumor-promoting inflammation in gastric cancers
- 주제(기타) Biochemistry & Molecular Biology
- 주제(기타) Medicine, Research & Experimental
- 설명문(일반) [Cho, Sung-Yup; Oh, Yumi; Jeong, Eui Man] Seoul Natl Univ, Dept Biochem & Mol Biol, Coll Med, Seoul, South Korea; [Cho, Sung-Yup; Chae, Jeesoo; Jong-Il Kim] Seoul Natl Univ, Dept Biomed Sci, Coll Med, Seoul, South Korea; [Cho, Sung-Yup; Lee, Hyuk-Joon; Jong-Il Kim; Yang, Han-Kwang] Seoul Natl Univ, Canc Res Inst, Coll Med, Seoul, South Korea; [Jeong, Eui Man] Seoul Natl Univ, Inst Human Environm Interface Biol, Coll Med, Seoul, South Korea; [Park, Sanghui] Ewha Womans Univ, Dept Pathol, Coll Med, Seoul, South Korea; [Lee, Dakeun] Ajou Univ, Dept Pathol, Sch Med, Suwon, South Korea; [Wang, Xiaorui; Zeng, Qiqi; Qin, Hongyu; Hu, Fang; Zhang, Chengsheng] Xi An Jiao Tong Univ, Precis Med Ctr, Affiliated Hosp 1, Xian, Peoples R China; [Gong, Hui; Liu, Xi; Zhang, Guanjun; Zhang, Chengsheng] Xi An Jiao Tong Univ, Dept Pathol, Affiliated Hosp 1, Xian, Peoples R China; [Na, Deukchae] Ewha Womans Univ, Ewha Inst Convergence Med, Mokdong Hosp, Seoul, South Korea; [Lee, Jieun; Lee, Charles] Ewha Womans Univ, Dept Life Sci, Seoul, South Korea; [Suh, Yun-Suhk; Kong, Seong-Ho; Lee, Hyuk-Joon; Yang, Han-Kwang] Seoul Natl Univ, Dept Surg, Coll Med, Seoul, South Korea; [Jong-Il Kim] Seoul Natl Univ, Med Res Ctr, Genom Med Inst GMI, Seoul, South Korea; [Park, Hansoo] Gwangju Inst Sci & Technol GIST, Dept Biomed Sci & Engn, Gwangju, South Korea; [Zhang, Chengsheng; Lee, Charles] Jackson Lab Genom Med, Farmington, CT 06032 USA
- 등재 SCIE, SCOPUS, KCI등재
- OA유형 Green Published, gold
- 발행기관 NATURE PUBLISHING GROUP
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000169330
- 본문언어 영어
- Published As https://dx.doi.org/10.1038/s12276-020-0444-7
- PubMed https://pubmed.ncbi.nlm.nih.gov/32467608
초록/요약
Stomach cancer: Enzyme promotes problematic inflammation An enzyme linked to harmful inflammation that promotes tumor growth could be a target for stomach cancer treatment. The expression of the enzyme transglutaminase 2 (TGM2) has been shown to increase in several types of cancer, but its precise role has been unclear. Sung-Yup Cho at Seoul National University College of Medicine, Korea and co-workers measured copy numbers and expression levels of TGM2 in gastric cancer cell lines and in tissue samples from patients undergoing gastrectomy. They found that higher levels of TGM2 were closely associated with increases in various genes that promote the recruitment and activity of tumor-associated macrophages, malfunctioning white blood cells that drive tumor-promoting inflammation. In addition, stomach cancer patients with higher expression of TGM2 had poorer prognoses, indicating the potential therapeutic value of targeting this enzyme. 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-1 beta-induced secretion of macrophage-recruiting chemokines and NF-kappa B 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.
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