Targeting the Microenvironment in Esophageal Cancer

Wang, Lei; Han, Huiqiong; Wang, Zehua; Shi, Litong; Yang, Mei; Qin, Yanru

doi:10.3389/fcell.2021.684966

Cited by 21 publications

(20 citation statements)

References 171 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cancer invasion and metastasis are not only determined by cancer cells but also by the tumor microenvironment (TME), with cancer-associated fibroblasts (CAFs) and the extracellular matrix (ECM) playing important roles during the progression of cancer ( 7 ). The TME also plays a critical role in ESCC ( 8 ). α-smooth muscle actin (α-SMA) is a marker of CAF activation, and the collagen I content in the stroma cells of the TME is correlated with the aggressiveness and outcome of tumors ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

IGFBP7 remodels the tumor microenvironment of esophageal squamous cell carcinoma by activating the TGFβ1/SMAD signaling pathway

Li¹,

Zhang

et al. 2022

Oncol Lett

View full text Add to dashboard Cite

Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer, and its development, growth, and invasiveness are regulated by the tumor microenvironment (TME). Insulin-like growth factor-binding protein-7 (IGFBP7), which is closely related to various tumors, transforming growth factor-β1 (TGFβ1), which is a key signal mediator in oncogenesis, α-smooth muscle actin (α-SMA), and collagen I are important components of the TME. IGFBP7 can upregulate the expression of TGFβ1 and activate the TGFβ1/SMAD signaling pathway, which leads to an increase in collagen I in hepatic stellate cells (HSCs). However, the contribution of IGFBP7 to TGFβ1 and the TME in the progression of ESCC remains unknown. In the present study, we investigated IGFBP7 expression and its effects on TGFβ1 and the TME in ESCC. A total of 45 patients were divided into three groups: early-tumor group (n=15), advanced-tumor group (n=15), and paracancer control group (n=15). The EC109 cell line was cultured and treated with AdIGFBP7 and LvshTGFβ1, and the expression levels of IGFBP7, TGFβ1, α-SMA, collagen I, and p-SMAD2/3 were determined by immunohistochemical staining and western blotting analysis. IGFBP7, TGFβ1, α-SMA, and collagen I were upregulated in the ESCC samples compared with the control samples (P<0.05), and the values peaked in the advanced-tumor group (P<0.05). Compared with the control group, the TGFβ1, α-SMA, p-SMAD2/3, and collagen I proteins were gradually increased from 24 to 72 h in the EC109 cells treated with AdIGFBP7 (P<0.05). Inhibition of TGFβ1 expression in the EC109 cells treated with AdIGFBP7 gradually reduced the expression of α-SMA, collagen I, and p-SMAD2/3 from 24 to 72 h (P<0.05). These findings suggest that increased IGFBP7 may accelerate the progression of ESCC by upregulating TGFβ1, α-SMA, and collagen I via activating the TGFβ1/SMAD signaling pathway, which could remodel the TME.

show abstract

Section: Introductionmentioning

confidence: 99%

IGFBP7 remodels the tumor microenvironment of esophageal squamous cell carcinoma by activating the TGFβ1/SMAD signaling pathway

Li¹,

Zhang

et al. 2022

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…However, the current survival rate of patients with GA remains low, even with the combined efforts of multidisciplinary teams. Over the years, tumor microenvironment has been the focus of our research ( 17 , 18 ), and chronic inflammation and immune dysfunction are its most important features ( 19 ). The release of various pro-inflammatory cytokines and inflammatory substances such as interleukin-1β, interleukin-8, and tumor necrosis factor-α promotes GA progression ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a nomogram for patients with stage II/III gastric adenocarcinoma after radical surgery

Wang

Han²,

Feng³

et al. 2022

Front. Surg.

Self Cite

View full text Add to dashboard Cite

BackgroundWe aimed to construct nomograms based on clinicopathological features and routine preoperative hematological indices to predict cancer-specific survival (CSS) and disease-free survival (DFS) in patients with stage II/III gastric adenocarcinoma (GA) after radical resection.MethodsWe retrospectively analyzed 468 patients with stage II/III GA after curative gastrectomy between 2012 and 2018; 70% of the patients were randomly assigned to the training set (n = 327) and the rest were assigned to the validation set (n = 141). The nomogram was constructed from independent predictors derived from the Cox regression in the training set. Using the consistency index, the calibration and the time-dependent receiver operating characteristic curves were used to evaluate the accuracy of the nomogram. Decision curve analysis was used to assess the value of the model in clinical applications. Patients were further divided into low- and high-risk groups based on the nomogram risk score.ResultsMultivariate Cox model identified depth of invasion, lymph node invasion, tumor differentiation, adjuvant chemotherapy, CA724, and platelet-albumin ratio as covariates associated with CSS and DFS. CA199 is a risk factor unique to CSS. The nomogram constructed using the results of the multivariate analysis showed high accuracy with a consistency index of 0.771 (CSS) and 0.771 (DFS). Moreover, the area under the curve values for the 3-and 5-year CSS were 0.868 and 0.918, and the corresponding values for DFS were 0.872 and 0.919, respectively. The nomogram had a greater clinical benefit than the TNM staging system. High-risk patients based on the nomogram had a worse prognosis than low-risk patients.ConclusionThe prognostic nomogram for patients with stage II/III GA after radical gastrectomy established in this study has a good predictive ability, which is helpful for doctors to accurately evaluate the prognosis of patients to make more reasonable treatment plans.

show abstract

“…Thus, TME is now regarded as a target-rich environment for the development of novel anticancer drugs in ESCC. Actually, many drugs that focus on diverse components of TME, including vascular endothelial growth factor (VEGF) and immune checkpoints, have been approved for clinical use ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of Tumor Microenvironment in Invasion and Metastasis of Esophageal Squamous Cell Carcinoma

2022

View full text Add to dashboard Cite

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in the world, with a high rate of morbidity. The invasion and metastasis of ESCC is the main reason for high mortality. More and more evidence suggests that metastasized cancer cells require cellular elements that contribute to ESCC tumor microenvironment (TME) formation. TME contains many immune cells and stromal components, which are critical to epithelial–mesenchymal transition, immune escape, angiogenesis/lymphangiogenesis, metastasis niche formation, and invasion/metastasis. In this review, we will focus on the mechanism of different microenvironment cellular elements in ESCC invasion and metastasis and discuss recent therapeutic attempts to restore the tumor-suppressing function of cells within the TME. It will represent the whole picture of TME in the metastasis and invasion process of ESCC.

show abstract

Targeting the Microenvironment in Esophageal Cancer

Cited by 21 publications

References 171 publications

IGFBP7 remodels the tumor microenvironment of esophageal squamous cell carcinoma by activating the TGFβ1/SMAD signaling pathway

IGFBP7 remodels the tumor microenvironment of esophageal squamous cell carcinoma by activating the TGFβ1/SMAD signaling pathway

Development and validation of a nomogram for patients with stage II/III gastric adenocarcinoma after radical surgery

The Role of Tumor Microenvironment in Invasion and Metastasis of Esophageal Squamous Cell Carcinoma

Contact Info

Product

Resources

About