scholarly journals Esophageal Squamous Cell Carcinoma Is Accompanied by Local and Systemic Changes in L-arginine/NO Pathway

2020 ◽  
Vol 21 (17) ◽  
pp. 6282 ◽  
Author(s):  
Iwona Bednarz-Misa ◽  
Paulina Fortuna ◽  
Mariusz G. Fleszar ◽  
Łukasz Lewandowski ◽  
Dorota Diakowska ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Metabolic Reprogramming ◽  
Enzyme Expression ◽  
Noncancerous Tissue ◽  
Immune Mediators ◽  
Esophageal Tumors ◽  
Therapy Target

The L-arginine/NO pathway holds promise as a source of potential therapy target and biomarker; yet, its status and utility in esophageal squamous cell carcinoma (ESCC) is unclear. We aimed at quantifying pathway metabolites in sera from patients with ESCC (n = 61) and benign conditions (n = 62) using LC-QTOF-MS and enzyme expression in esophageal tumors and matched noncancerous samples (n = 40) using real-time PCR with reference to ESCC pathology and circulating immune/inflammatory mediators, quantified using Luminex xMAP technology. ESCC was associated with elevated systemic arginine and asymmetric dimethylarginine. Citrulline decreased and arginine bioavailability increased along with increasing ESCC advancement. Compared to adjacent tissue, tumors overexpressed ODC1, NOS2, PRMT1, and PRMT5 but had downregulated ARG1, ARG2, and DDAH1. Except for markedly higher NOS2 and lower ODC1 in tumors from M1 patients, the pathology-associated changes in enzyme expression were subtle and present also in noncancerous tissue. Both the local enzyme expression level and systemic metabolite concentration were related to circulating inflammatory and immune mediators, particularly those associated with eosinophils and those promoting viability and self-renewal of cancer stem cells. Metabolic reprogramming in ESCC manifests itself by the altered L-arginine/NO pathway. Upregulation of PRMTs in addition to NOS2 and ODC1 and the pathway link with stemness-promoting cytokines warrants further investigation.

scholarly journals Immunosuppressive phenotype of esophagus tumors stroma

2020 ◽  
Author(s):  
Alexei Gratchev ◽  
Olga V. Kovaleva ◽  
Madina A. Rashidova ◽  
Daria V. Samoilova ◽  
Valeria V. Mochalnikova
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Survival Data ◽  
Immunohistochemical Analysis ◽  
Good Prognosis ◽  
Disease Stage ◽  
Rank Test ◽  
Esophageal Tumors

Abstract Background Tumor associated macrophages and tumor infiltrating lymphocytes contribute significantly to the development of immunosuppressive properties of tumor. In this study we performed immunohistochemical analysis of immune cells of esophageal tumors stroma. Methods Paraffin‑embedded tissue specimens from 48 esophageal squamous cell carcinoma patients were retrospectively collected for immunohistochemical analysis of stromal cells. For staining of macrophages, CD68, CD163, CD206, PU.1 and iNOS were used. For T-cells detection CD8, CD3, FOXP3 were used. As well we performed staining for PD-L1 that can be expressed on tumor associated macrophagesand tumor cells. Clinicopathological and survival data were collected and analyzed using the χ2 and Fisher exact tests, Kaplan–Meier curves, and the log‑rank test. The correlation analysis was performed with Spearman correlation coefficient. Results The level of CD206 expression was associated with histological grade (p = 0.034), FOXP3 expression was associated with sex and age (p = 0.041, p = 0.003 respectively) and iNOS expression was associated with the disease stage (p = 0.044). In addition, FOXP3 and CD163 appeared to be markers of good prognosis (HR = 0.5407, p = 0.0462; HR = 0.4447, p = 0.0456 respectively). Significant association between PU.1 + and CD68 + macrophages (r = 0.752; P = 0.000) and between PU.1 + and CD163 + macrophages (r = 0.585; P = 0.000) was established, positive association between PU.1 and CD206 expression was also observed (r = 0.424; P = 0.001). Conclusions Large amounts of CD163 + macrophages and FOXP3+ Т-cells appear to be markers of good prognosis of esophageal squamous cell carcinoma. The number of PU.1 + macrophages strongly correlate with the number of CD68 + macrophages therefore usage of PU.1 as a potential macrophage marker can be recommended esophageal tumors.

scholarly journals NRF2/ACSS2 axis mediates the metabolic effect of alcohol drinking on esophageal squamous cell carcinoma

2020 ◽  
Vol 477 (16) ◽  
pp. 3075-3089
Author(s):  
Joab Otieno Odera ◽  
Zhaohui Xiong ◽  
Caizhi Huang ◽  
Ning Gu ◽  
Wenjun Yang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Alcohol Drinking ◽  
Molecular Mechanisms ◽  
Ethanol Exposure ◽  
Metabolic Effect ◽  
Metabolic Reprogramming ◽  
Acetyl Coa

Alcohol drinking is a leading risk factor for the development of esophageal squamous cell carcinoma (ESCC). However, the molecular mechanisms of alcohol-associated ESCC remain poorly understood. One of the most commonly mutated genes in ESCC is nuclear factor erythroid 2 like 2 (NFE2L2 or NRF2), which is a critical transcription factor regulating oxidative stress response and drug detoxification. When NRF2 is hyperactive in cancer cells, however, it leads to metabolic reprogramming, cell proliferation, chemoradioresistance, and poor prognosis. In this study, hyperactive NRF2 was found to up-regulate acetyl-CoA synthetase short-chain family members 2 (ACSS2), an enzyme that converts acetate to acetyl-CoA, in ESCC cells and mouse esophagus. We also showed that knockdown of NRF2 or ACSS2 led to decreased ACSS2 expression, which in turn reduced the levels of acetyl-CoA and ATP with or without ethanol exposure. In addition, ethanol exposure enhanced lipid synthesis in ESCC cells. Moreover, we observed a change in the metabolic profile of ESCC cells exposed to ethanol as a result of their NRF2 or ACSS2 status. We further showed that ACSS2 contributed to the invasive capability of NRF2high ESCC cells exposed to ethanol. In conclusion, the NRF2/ACSS2 axis mediates the metabolic effect of alcohol drinking on ESCC.

scholarly journals Metabolomic Characterization Reveals ILF2 and ILF3 Affected Metabolic Adaptions in Esophageal Squamous Cell Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Bin Zang ◽  
Wen Wang ◽  
Yiqian Wang ◽  
Pengfei Li ◽  
Tian Xia ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Acid Metabolism ◽  
Metabolic Reprogramming ◽  
Chain Acyl ◽  
Glycolysis Pathway ◽  
Cancer Tissues

Esophageal cancer (EC) is a common malignant disease in eastern countries. However, a study of the metabolomic characteristics associated with other biological factors in esophageal squamous cell carcinoma (ESCC) is limited. Interleukin enhancer binding factor 2 (ILF2) and ILF3, double-stranded RNA-binding proteins, have been reported to contribute to the occurrence and development of various types of malignancy. Nevertheless, the underlying functions of ILF2 and ILF3 in ESCC metabolic reprogramming have never been reported. This study aimed to contribute to the metabolic characterization of ESCC and to investigate the metabolomic alterations associated with ILF2 and ILF3 in ESCC tissues. Here, we identified 112 differential metabolites, which were mainly enriched in phosphatidylcholine biosynthesis, fatty acid metabolism, and amino acid metabolism pathways, based on liquid chromatography–mass spectrometry and capillary electrophoresis–mass spectrometry approaches using ESCC tissues and paired para-cancer tissues from twenty-eight ESCC patients. In addition, ILF2 and ILF3 expression were significantly elevated in EC tissues compared to the histologically normal samples, and closely associated with PI3K/AKT and MAPK signaling pathways in ESCC. Moreover, in ESCC tissues with a high ILF2 expression, several short-chain acyl-carnitines (C3:0, C4:0, and C5:0) related to the BCAA metabolic pathway and long-chain acyl-carnitines (C14:0, C16:0, C16:0-OH, and C18:0) involved in the oxidation of fatty acids were obviously upregulated. Additionally, a series of intermediate metabolites involved in the glycolysis pathway, including G6P/F6P, F1,6BP, DHAP, G3P, and 2,3BPG, were remarkably downregulated in highly ILF3-expressed ESCC tissues compared with the corresponding para-cancer tissues. Overall, these findings may provide evidence for the roles of ILF2 and ILF3 during the process of ESCC metabolic alterations, and new insights into the development of early diagnosis and treatment for ESCC. Further investigation is needed to clarify the underlying mechanism of ILF2 and ILF3 on acyl-carnitines and the glycolysis pathway, respectively.

Progress of Chemoradiotherapy for Resectable Esophageal Squamous Cell Carcinoma

2012 ◽  
Vol 63 (2) ◽  
pp. 195-195
Author(s):  
K. Minashi ◽  
T. Yano ◽  
T. Kojima ◽  
M. Onozawa ◽  
K. Nihei ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Resectable Esophageal
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