CXCR1 promotes malignant behavior of gastric cancer cells in vitro and in vivo in AKT and EKR1/2 phosphorylation

Wang, Junpu; Hu, Wanming; Wu, Xiaoying; Wang, Kuansong; Yu, Jun; Luo, Binghui; Luo, Guopei; Wang, Weiyuan; Wang, Huiling; Li, Jinghe; Wen, Ji

doi:10.3892/ijo.2016.3428

Cited by 19 publications

(17 citation statements)

References 33 publications

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“…Tumor angiogenesis is a crucial aspect in tumor proliferation and metastasis particularly when tumors diameter approximates 2 mm 22 . It has been reported that chemokine receptors play an important role in tumor angiogenesis, such as CXCR1 and CXCR2 23 , 24 . CCR4 and its ligands contributed to vascular structure formation through the mobilization of smooth muscle precursor cells 25 .…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of chemokine receptor CCR4 is associated with Human Hepatocellular Carcinoma malignant behavior

Cheng

Jin

et al. 2017

Sci Rep

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Studies indicate that the chemokine receptor is responsible for poor prognosis of hepatocellular carcinoma (HCC) patients. In this study, we initially demonstrated that CCR4 is overexpressed in HCC specimens, and its elevation in HCC tissues positively correlates with tumor capsule breakthrough and vascular invasion. Although overexpression of CCR4 failed to influent proliferation of HCC cells in vitro apparently, the prominent acceleration on HCC tumor growth in vivo was remarkable. The underlying mechanism may be involved in neovascularization. Interestingly, different from effect on proliferation, CCR4 overexpression could trigger HCC metastasis both in vitro and in vivo also induced HCC cell epithelial-mesenchymal transition (EMT) as well. Then we identified matrix metalloproteinase 2 (MMP2) as a direct target of CCR4 which plays an important role in CCR4-mediated HCC cell invasion, which was up-regulated by ERK/AKT signaling. Positive correlation between CCR4 and MMP2 expression was also observed in HCC tissues. In conclusion, our study suggested that chemokine receptor CCR4 promotes HCC malignancy and facilitated HCC cell metastases via ERK/AKT/MMP2 pathway. These findings suggest that CCR4 may be a potential new diagnostic and prognostic marker in HCC, and targeting CCR4 may be a potential therapeutic option for blocking HCC metastasis.

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Section: Discussionmentioning

confidence: 99%

Up-regulation of chemokine receptor CCR4 is associated with Human Hepatocellular Carcinoma malignant behavior

Cheng

Jin

et al. 2017

Sci Rep

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“…The analysis of Proliferation, differentiation and metabolism Cluster ( Supplementary Table 6 ) revealed among others, the overexpression of several genes involved in invasion and metastasis of gastric cancer including CXCR1, that promotes malignant behavior of gastric cancer cells in vitro and in vivo inducing AKT and ERK1/2 phosphorylation ( 110 , 111 ), FPR2, that induces invasion and metastasis of gastric cancer cells and predicts the prognosis of patients acting as a novel prognostic marker ( 112 ), CARD14, involved in the progression from normal gastric epithelial to gastric cancer ( 113 ). Finally, we found also a decreased expression of CLDN11, whose silencing is associated with increased invasiveness of gastric cancer cells ( 114 ).…”

Section: Resultsmentioning

confidence: 99%

Analysis of Gastric Cancer Transcriptome Allows the Identification of Histotype Specific Molecular Signatures With Prognostic Potential

et al. 2021

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Gastric cancer is the fifth most common malignancy but the third leading cause of cancer-associated mortality worldwide. Therapy for gastric cancer remain largely suboptimal making the identification of novel therapeutic targets an urgent medical need. In the present study we have carried out a high-throughput sequencing of transcriptome expression in patients with gastric cancers. Twenty-four patients, among a series of 53, who underwent an attempt of curative surgery for gastric cancers in a single center, were enrolled. Patients were sub-grouped according to their histopathology into diffuse and intestinal types, and the transcriptome of the two subgroups assessed by RNAseq analysis and compared to the normal gastric mucosa. The results of this investigation demonstrated that the two histopathology phenotypes express two different patterns of gene expression. A total of 2,064 transcripts were differentially expressed between neoplastic and non-neoplastic tissues: 772 were specific for the intestinal type and 407 for the diffuse type. Only 885 transcripts were simultaneously differentially expressed by both tumors. The per pathway analysis demonstrated an enrichment of extracellular matrix and immune dysfunction in the intestinal type including CXCR2, CXCR1, FPR2, CARD14, EFNA2, AQ9, TRIP13, KLK11 and GHRL. At the univariate analysis reduced levels AQP9 was found to be a negative predictor of 4 years survival. In the diffuse type low levels CXCR2 and high levels of CARD14 mRNA were negative predictors of 4 years survival. In summary, we have identified a group of genes differentially regulated in the intestinal and diffuse histotypes of gastric cancers with AQP9, CARD14 and CXCR2 impacting on patients’ prognosis, although CXCR2 is the only factor independently impacting overall survival.

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“…The role of CXCR1/2 -CXCL8 interaction with cancer has been studied from different perspectives including migration of neutrophils, TAMS, and CXCR1/2+ cancer cells to tumor sites [ 139 , 140 ] angiogenesis [ 141 ], and tumor stemness [ 142 ]. Altogether this makes the CXCR1/2 -CXCL8 pathway a target for cancer therapy [ 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 ]. Breast cancer is among the most relevant human diseases for the blockade of the CXCL8-CXCR1/2 interaction since CXCL8 is up-regulated in breast cancer patients is associated with poor prognosis [ 148 , 149 ], and CXCL8 drives tumor stemness and angiogenesis [ 146 , 150 , 151 , 152 ].…”

Section: Key Chemokine-chemokine Receptor Interactions That Support Tumor Growthmentioning

confidence: 99%

“…Currently, the extension of this study to human clinical trials is ongoing [ 153 ]. This therapy might be relevant to other cancers among them: gastric cancer [ 145 , 154 , 155 ], melanoma [ 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 ], and others.…”

Section: Key Chemokine-chemokine Receptor Interactions That Support Tumor Growthmentioning

confidence: 99%

Chemokines in the Landscape of Cancer Immunotherapy: How They and Their Receptors Can Be Used to Turn Cold Tumors into Hot Ones?

Karin

2021

Cancers

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Over the last decade, monoclonal antibodies to immune checkpoint inhibitors (ICI), also known as immune checkpoint blockers (ICB), have been the most successful approach for cancer therapy. Starting with mAb to cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors in metastatic melanoma and continuing with blockers of the interactions between program cell death 1 (PD-1) and its ligand program cell death ligand 1 (PDL-1) or program cell death ligand 2 (PDL-2), that have been approved for about 20 different indications. Yet for many cancers, ICI shows limited success. Several lines of evidence imply that the limited success in cancer immunotherapy is associated with attempts to treat patients with “cold tumors” that either lack effector T cells, or in which these cells are markedly suppressed by regulatory T cells (Tregs). Chemokines are a well-defined group of proteins that were so named due to their chemotactic properties. The current review focuses on key chemokines that not only attract leukocytes but also shape their biological properties. CXCR3 is a chemokine receptor with 3 ligands. We suggest using Ig-based fusion proteins of two of them: CXL9 and CXCL10, to enhance anti-tumor immunity and perhaps transform cold tumors into hot tumors. Potential differences between CXCL9 and CXCL10 regarding ICI are discussed. We also discuss the possibility of targeting the function or deleting a key subset of Tregs that are CCR8+ by monoclonal antibodies to CCR8. These cells are preferentially abundant in several tumors and are likely to be the key drivers in suppressing anti-cancer immune reactivity.

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CXCR1 promotes malignant behavior of gastric cancer cells in vitro and in vivo in AKT and EKR1/2 phosphorylation

Cited by 19 publications

References 33 publications

Up-regulation of chemokine receptor CCR4 is associated with Human Hepatocellular Carcinoma malignant behavior

Up-regulation of chemokine receptor CCR4 is associated with Human Hepatocellular Carcinoma malignant behavior

Analysis of Gastric Cancer Transcriptome Allows the Identification of Histotype Specific Molecular Signatures With Prognostic Potential

Chemokines in the Landscape of Cancer Immunotherapy: How They and Their Receptors Can Be Used to Turn Cold Tumors into Hot Ones?

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