Novel role of granulocyte-macrophage colony-stimulating factor: antitumor effects through inhibition of epithelial-to-mesenchymal transition in esophageal cancer

Zhang, Jingxin; Liu, Qiqi; Qiao, Lili; Hu, Pingping; Deng, Guohua; Liang, Ning; Xie, Jian; Luo, Hui; Zhang, Jiandong

doi:10.2147/ott.s133504

Cited by 4 publications

(3 citation statements)

References 46 publications

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“…In agreement with the present study, anti-cancer roles of GM-CSF are shown in colon (COLO 205) ( Nebiker et al, 2014 ), prostate (patient tissues) ( Wei et al, 2016 ), CCA (KKU-213A) ( Panya et al, 2018 ), bladder (MGHU3, UMUC3) ( Hori et al, 2019 ), cervical (patient tissues) ( Jiang et al, 2015 ) and esophageal cancers (Eca-109, EC9706) ( Zhang et al, 2017 ), through activations of CD16-positive monocytes and effector T-cells, but suppressions of M2-mediated angiogenesis and pro-inflammatory mediator productions ( e.g. , cyclooxygenase-2 and inducible nitric oxide synthase).…”

Section: Discussionsupporting

confidence: 91%

“…Regarding the cancer milieu, the controversial roles of GM-CSF were demonstrated. Cancer-promoting functions are established in breast, glioma, liver, and pancreatic cancers ( Bayne et al, 2012 ; Kohanbash et al, 2013 ; Lin et al, 2017 ; Reggiani et al, 2017 ; Revoltella, Menicagli & Campani, 2012 ), whereas cancer-preventing roles are demonstrated in bladder, cervical, colon, esophageal, and prostate cancers ( Hori et al, 2019 ; Jiang et al, 2015 ; Nebiker et al, 2014 ; Wei et al, 2016 ; Zhang et al, 2017 ). In CCA, there is a report demonstrating that cirrhosis-related iCCA-derived GM-CSF promotes intense neutrophil infiltration ( Sasaki et al, 2003 ); however, the contradictory result is demonstrated in the spontaneous iCCA mouse model.…”

Section: Introductionmentioning

confidence: 99%

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Dense GM-CSFRα-expressing immune infiltration is allied with longer survival of intrahepatic cholangiocarcinoma patients

Saranaruk

Waraasawapati

Chamgramol

et al. 2023

PeerJ

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Background Intrahepatic cholangiocarcinoma (iCCA) is a cancer arising from intrahepatic bile duct epithelium. An iCCA incidence is increasing worldwide; however, the outcome of the disease is dismal. The linkage between chronic inflammation and iCCA progression is well established, but the roles of granulocyte-macrophage colony-stimulating factor (GM-CSF) remain unrevealed. Thus, a better understanding of GM-CSF functions in CCA may provide an alternative approach to CCA treatment. Methods Differential GM-CSF and GM-CSFRα mRNA expressions in CCA tissues were investigated by Gene Expression Profiling Interactive Analysis (GEPIA) based on The Cancer Genome Atlas (TCGA) database. The protein expressions and localizations of GM-CSF and its cognate receptor (GM-CSFRα) in iCCA patients’ tissues were demonstrated by the immunohistochemistry (IHC) techniques. The survival analyses were performed using Kaplan-Meier survival analysis with log-rank test and Cox proportional hazard regression model for multivariate analysis. The GM-CSF productions and GM-CSFRα expressions on CCA cells were assessed by ELISA and flow cytometry. The effects of GM-CSF on CCA cell proliferation and migration were evaluated after recombinant human GM-CSF treatment. The relationship between GM-CSF or GM-CSFRα level and related immune cell infiltration was analyzed using the Tumor Immune Estimation Resource (TIMER). Results GEPIA analysis indicated GM-CSF and GM-CSFRα expressions were higher in CCA tissues than in normal counterparts, and high GM-CSFRα was related to the longer disease-free survival of the patients (p < 0.001). IHC analysis revealed that CCA cells differentially expressed GM-CSF, while GM-CSFRα was expressed on cancer-infiltrating immune cells. The patient whose CCA tissue contained high GM-CSF expressed CCA, and moderate to dense GM-CSFRα-expressing immune cell infiltration (ICI) acquired longer overall survival (OS) (p = 0.047), whereas light GM-CSFRα-expressing ICI contributed to an increased hazard ratio (HR) to 1.882 (95% CI [1.077–3.287]; p = 0.026). In non-papillary subtype, an aggressive CCA subtype, patients with light GM-CSFRα-expressing ICI had shorter median OS (181 vs. 351 days; p = 0.002) and the HR was elevated to 2.788 (95% CI [1.299–5.985]; p = 0.009). Additionally, TIMER analysis demonstrated GM-CSFRα expression was positively correlated with neutrophil, dendritic cell, and CD8+ T cell infiltrations, though it was conversely related to M2-macrophage and myeloid-derived suppressor cell infiltration. However, the direct effects of GM-CSF on CCA cell proliferation and migration were not observed in the current study. Conclusions Light GM-CSFRα-expressing ICI was an independent poor prognostic factor for iCCA patients. Anti-cancer functions of GM-CSFRα-expressing ICI were suggested. Altogether, the benefits of acquired GM-CSFRα-expressing ICI and GM-CSF for CCA treatment are proposed herein and require elucidation.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Dense GM-CSFRα-expressing immune infiltration is allied with longer survival of intrahepatic cholangiocarcinoma patients

Saranaruk

Waraasawapati

Chamgramol

et al. 2023

PeerJ

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“…Based on previous reports suggesting that CSF2 could inhibit the development of cancer (13)(14)(15)67), we further investigated the serum samples from patients with EC, CRC, GC, LC, and MC. The s-CSF2-Ab levels were significantly higher in patients with EC, CRC, GC, and LC, but not in those with MC, compared with HDs (Figure 5; Table 7).…”

Section: Elevated S-csf2-ab Levels In Patients With Cancermentioning

confidence: 99%

Utility of atherosclerosis-associated serum antibodies against colony-stimulating factor 2 in predicting the onset of acute ischemic stroke and prognosis of colorectal cancer

Yoshida

Kubota

et al. 2023

Front. Cardiovasc. Med.

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IntroductionAutoantibodies against inflammatory cytokines may be used for the prevention of atherosclerosis. Preclinical studies consider colony-stimulating factor 2 (CSF2) as an essential cytokine with a causal relationship to atherosclerosis and cancer. We examined the serum anti-CSF2 antibody levels in patients with atherosclerosis or solid cancer.MethodsWe measured the serum anti-CSF2 antibody levels via amplified luminescent proximity homogeneous assay-linked immunosorbent assay based on the recognition of recombinant glutathione S-transferase-fused CSF2 protein or a CSF2-derived peptide as the antigen.ResultsThe serum anti-CSF2 antibody (s-CSF2-Ab) levels were significantly higher in patients with acute ischemic stroke (AIS), acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic kidney disease (CKD) compared with healthy donors (HDs). In addition, the s-CSF2-Ab levels were associated with intima-media thickness and hypertension. The analyzes of samples obtained from a Japan Public Health Center-based prospective study suggested the utility of s-CSF2-Ab as a risk factor for AIS. Furthermore, the s-CSF2-Ab levels were higher in patients with esophageal, colorectal, gastric, and lung cancer than in HDs but not in those with mammary cancer. In addition, the s-CSF2-Ab levels were associated with unfavorable postoperative prognosis in colorectal cancer (CRC). In CRC, the s-CSF2-Ab levels were more closely associated with poor prognosis in patients with p53-Ab-negative CRC despite the lack of significant association of the anti-p53 antibody (p53-Ab) levels with the overall survival.ConclusionS-CSF2-Ab was useful for the diagnosis of atherosclerosis-related AIS, AMI, DM, and CKD and could discriminate poor prognosis, especially in p53-Ab-negative CRC.

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Protein arginine methyltransferase 5: a potential cancer therapeutic target

Yuan

Nie

2021

Cell Oncol.

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Novel role of granulocyte-macrophage colony-stimulating factor: antitumor effects through inhibition of epithelial-to-mesenchymal transition in esophageal cancer

Cited by 4 publications

References 46 publications

Dense GM-CSFRα-expressing immune infiltration is allied with longer survival of intrahepatic cholangiocarcinoma patients

Dense GM-CSFRα-expressing immune infiltration is allied with longer survival of intrahepatic cholangiocarcinoma patients

Utility of atherosclerosis-associated serum antibodies against colony-stimulating factor 2 in predicting the onset of acute ischemic stroke and prognosis of colorectal cancer

Protein arginine methyltransferase 5: a potential cancer therapeutic target

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