Amplification of transglutaminase 2 enhances tumor-promoting inflammation in gastric cancers.

Cell Line, Tumor Computational Biology / methods GTP-Binding Proteins / genetics Gene Amplification Gene Dosage Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Inflammation / genetics Prognosis Protein Glutamine gamma Glutamyltransferase 2 Stomach Neoplasms / genetics Transcriptome Transglutaminases / genetics Tumor Microenvironment / genetics Tumor-Associated Macrophages / immunology

Journal

Experimental & molecular medicine

ISSN: 2092-6413

Titre abrégé: Exp Mol Med

Pays: United States

ID NLM: 9607880

Informations de publication

Date de publication:
05 2020

Historique:

received: 26 02 2020

accepted: 06 04 2020

revised: 05 04 2020

pubmed: 30 5 2020

medline: 31 7 2021

entrez: 30 5 2020

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s12276-020-0444-7 PMID: 32467608 PMC: PMC7272405

pubmed: 32467608

doi: 10.1038/s12276-020-0444-7

pii: 10.1038/s12276-020-0444-7

pmc: PMC7272405

doi:

Substances chimiques

TGM2 protein, human 0

Protein Glutamine gamma Glutamyltransferase 2 EC 2.3.2.13

Transglutaminases EC 2.3.2.13

GTP-Binding Proteins EC 3.6.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

854-864

Subventions

Organisme : National Research Foundation of Korea (NRF)

ID : 2017R1C1B2002183

Pays : International

Organisme : National Research Foundation of Korea (NRF)

ID : 2015K1A4A3047851

Pays : International

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