Systematic review and meta-analysis of the prognostic value of CXCR2 in solid tumor patients

Yong, Yang; Luo, Baoyang; An, Yong; Sun, Hongli; Cai, Haibo; Sun, Donglin

doi:10.18632/oncotarget.22285

Cited by 13 publications

(15 citation statements)

References 50 publications

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“…IL-17, thus, up-regulates the expression of CXCR2 ligands, promoting the recruitment of cancerpromoting neutrophils. These findings also explain why higher levels of CXCR2 ligands and IL-17 are associated with lower survival rates in cancer patients 23,43,44 and suggest why patients who develop resistance to chemotherapy have lower survival rates. The data also suggest that…”

Section: Discussionmentioning

confidence: 78%

IL-17–CXC Chemokine Receptor 2 Axis Facilitates Breast Cancer Progression by Up-Regulating Neutrophil Recruitment

Awaji

Saxena

et al. 2020

The American Journal of Pathology

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Recent evidence suggests that interactions among proinflammatory cytokines, chemokines, and cancer cellerecruited neutrophils result in enhanced metastasis and chemotherapy resistance. Nonetheless, the detailed mechanism remains unclear. Our aim was to discover the role of IL-17, CXC chemokine receptor 2 (CXCR2) ligands, and cancer-associated neutrophils in chemotherapy resistance and metastasis in breast cancer. Mice were injected with Cl66 murine mammary tumor cells, Cl66 cells resistant to doxorubicin (Cl66-Dox), or Cl66 cells resistant to paclitaxel (Cl66-Pac). Higher levels of IL-17 receptor, CXCR2 chemokines, and CXCR2 were observed in tumors generated from Cl66-Dox and Cl66-Pac cells in comparison with tumors generated from Cl66 cells. Tumors generated from Cl66-Dox and Cl66-Pac cells had higher infiltration of neutrophils and T helper 17 cells. In comparison with primary tumor sites, there were increased levels of CXCR2, CXCR2 ligands, and IL-17 receptor within the metastatic lesions. Moreover, IL-17 increased the expression of CXCR2 ligands and cell proliferation of Cl66 cells. The supernatant of Cl66-Dox and Cl66-Pac cells enhanced neutrophil chemotaxis. In addition, IL-17einduced neutrophil chemotaxis was dependent on CXCR2 signaling. Collectively, these data demonstrate that the IL-17eCXCR2 axis facilitates the recruitment of neutrophils to the tumor sites, thus allowing them to play a cancer-promoting role in cancer progression.

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Section: Discussionmentioning

confidence: 78%

IL-17–CXC Chemokine Receptor 2 Axis Facilitates Breast Cancer Progression by Up-Regulating Neutrophil Recruitment

Awaji

Saxena

et al. 2020

The American Journal of Pathology

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“…The percentage of pixels in each biopsy that had a value above this threshold was calculated and biopsies with any percentage above 0 were marked as high expression of GPR39. The numbers of positive GPR39- expressing biopsies versus negative expressing biopsies was determined, and the tissues were classified as grade 2 or 3 and ER negative or positive expression, as done previously 73 . We then performed a Fisher analysis for the slides that exhibited negative or positive ER, separately, and determined the significance of the difference between grade 2 and 3 that were with or without GPR39 expression.…”

Section: Methodsmentioning

confidence: 99%

Enhanced ZnR/GPR39 Activity in Breast Cancer, an Alternative Trigger of Signaling Leading to Cell Growth

Ventura-Bixenshpaner

Asraf

Chakraborty

et al. 2018

Sci Rep

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Acquired resistance to the estrogen receptor (ER) antagonist tamoxifen, is a major obstacle in treatment of breast cancer. Changes in Zn2+ accumulation and distribution are associated with tamoxifen-resistance and breast cancer progression. The Zn2+-sensing G-protein coupled receptor, ZnR/GPR39, triggers signaling leading to cell growth, but a role for this receptor in breast cancer in unknown. Using fluorescence imaging, we found Zn2+-dependent Ca2+ release, mediated by ZnR/GPR39 activity, in TAMR tamoxifen-resistant cells derived from MCF-7 cells, but not in ER-expressing MCF-7 or T47D cells. Furthermore, ZnR/GPR39 signaling was monitored in ER negative BT20, MDA-MB-453 and JIMT-1 cells. Expression of ZnR/GPR39 was increased in grade 3 human breast cancer biopsies compared to grade 2. Consistently, analysis of two breast cancer patient cohorts, GDS4057 and TCGA, indicated that in ER-negative tumors higher ZnR/GPR39 mRNA levels are associated with more aggressive tumors. Activation of ZnR/GPR39 in TAMR cells triggered MAPK, mTOR and PI3K signaling. Importantly, enhanced cell growth and invasiveness was observed in the ER negative breast cancer cells, TAMR, MDA-MB-453 and BT20 cells but not in the ER expressing MCF-7 cells. Thus, we suggest ZnR/GPR39 as a potential therapeutic target for combination treatment in breast cancer, particularly relevant in ER negative tumors.

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“…CXCR2 also induces the migration of MDSCs, thus, promoting local immunosuppression ( 107 ). Studies show that cancer patients with high levels of CXCR2 have low overall survival and poor prognosis ( 108 ). The CXCL8-CXCR2 axis can also stimulate the transcription of VEGF and activate its receptor,VEGFR2, in endothelial cells by the NF-κB pathway ( 109 ).…”

Section: Chemokines and Chemokine Receptorsmentioning

confidence: 99%

Tackling Immune Targets for Breast Cancer: Beyond PD-1/PD-L1 Axis

et al. 2021

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The burden of breast cancer is imposing a huge global problem. Drug discovery research and novel approaches to treat breast cancer have been carried out extensively over the last decades. Although immune checkpoint inhibitors are showing promising preclinical and clinical results in treating breast cancer, they are facing multiple limitations. From an immunological perspective, a recent report highlighted breast cancer as an “inflamed tumor” with an immunosuppressive microenvironment. Consequently, researchers have been focusing on identifying novel immunological targets that can tune up the tumor immune microenvironment. In this context, several novel non-classical immune targets have been targeted to determine their ability to uncouple immunoregulatory pathways at play in the tumor microenvironment. This article will highlight strategies designed to increase the immunogenicity of the breast tumor microenvironment. It also addresses the latest studies on targets which can enhance immune responses to breast cancer and discusses examples of preclinical and clinical trial landscapes that utilize these targets.

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Systematic review and meta-analysis of the prognostic value of CXCR2 in solid tumor patients

Cited by 13 publications

References 50 publications

IL-17–CXC Chemokine Receptor 2 Axis Facilitates Breast Cancer Progression by Up-Regulating Neutrophil Recruitment

IL-17–CXC Chemokine Receptor 2 Axis Facilitates Breast Cancer Progression by Up-Regulating Neutrophil Recruitment

Enhanced ZnR/GPR39 Activity in Breast Cancer, an Alternative Trigger of Signaling Leading to Cell Growth

Tackling Immune Targets for Breast Cancer: Beyond PD-1/PD-L1 Axis

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