scholarly journals Correction: CXCR2 expression on granulocyte and macrophage progenitors under tumor conditions contributes to mo-MDSC generation via SAP18/ERK/STAT3

2019 ◽  
Vol 10 (9) ◽  
Author(s):  
Xiaoqing Han ◽  
Huifang Shi ◽  
Yingying Sun ◽  
Chao Shang ◽  
Tao Luan ◽  
...  
Keyword(s):  
Cxcr2 Expression

scholarly journals High CXCR2 expression predicts poor prognosis in adult patients with acute myeloid leukemia

2020 ◽  
Vol 11 ◽  
pp. 204062072095858
Author(s):  
Wei Tang ◽  
Zunyan Li ◽  
Xian Li ◽  
Zhonghua Huo
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Mononuclear Cells ◽  
Cox Proportional Hazards ◽  
Adult Patients ◽  
The Cancer Genome Atlas ◽  
Clinical Parameters ◽  
Cxcr2 Expression ◽  
Acute Myeloid

Aims: This study aimed to assess the associations between clinical parameters, long-term outcomes, and expression of chemokine receptor CXCR2 in patients with acute myeloid leukemia (AML). Methods: From May 2013 to May 2017, 83 adult patients newly diagnosed with AML in the Affiliated Hospital of BeiHua University and Jilin Chemical Hospital, were enrolled in this study. The expression of CXCR2 in bone marrow mononuclear cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Clinical information and RNA-sequencing datasets of The Cancer Genome Atlas (TCGA) ( n = 136) were obtained. The associations between clinical parameters, prognosis, and CXCR2 expression were analyzed. Results: From both cohorts, patients with AML with M4 and M5 subtypes showed higher CXCR2 expression levels than those with other French-American-British (FAB) subtypes. Patients with extramedullary leukemia infiltration had higher CXCR2 levels than those without. In our cohort, patients with high CXCR2 levels (⩾2.099) had lower relapse-free survival (RFS) ( p < 0.000001) and overall survival (OS) ( p = 0.000107) than those with low levels (<2.099). High CXCR2 levels (⩾2.082) also indicated a poor OS in the TCGA cohort but only in patients younger than 65 years (5-year OS: 7.7% versus 29.9% in those with CXCR2 levels < 2.082). High CXCR2 levels independently predicted poor prognosis in AML patients, as determined by Cox proportional hazards models. Conclusion: Our results suggest that high CXCR2 expression associates with the monocytic lineage of AML and is an independent risk factor for poor patient prognosis.

scholarly journals IL8-CXCR2 pathway inhibition as a therapeutic strategy against MDS and AML stem cells

Blood ◽  
2015 ◽  
Vol 125 (20) ◽  
pp. 3144-3152 ◽  
Author(s):  
Carolina Schinke ◽  
Orsolya Giricz ◽  
Weijuan Li ◽  
Aditi Shastri ◽  
Shanisha Gordon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Therapeutic Strategy ◽  
In Vivo Models ◽  
Cxcr2 Expression ◽  
Key Points ◽  
Pathway Inhibition ◽  
Worse Prognosis

Key Points IL8-CXCR2 is overexpressed in purified stem cells from AML and MDS, and CXCR2 expression is associated with worse prognosis. Inhibition of CXCR2 by genetic and pharmacologic means leads to decreased viability in AML/MDS stem cells and in vitro and in vivo models.

Interleukin-8 and CXCR2 expression in spindle cell haemangioendothelioma

2008 ◽  
Vol 22 (5) ◽  
pp. 638-640 ◽  
Author(s):  
H Sato ◽  
T Takahashi ◽  
Y Fujisawa ◽  
Y Nakamura ◽  
H Enomoto ◽  
...  
Keyword(s):  
Spindle Cell ◽  
Interleukin 8 ◽  
Cxcr2 Expression

Inhibition Of CXCR2 As a Therapeutic Strategy In AML and MDS

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 484-484 ◽  
Author(s):  
Carolina Schinke ◽  
Orsolya Giricz ◽  
Shanisha A. K. Gordon ◽  
Laura Barreyro ◽  
Tushar D. Bhagat ◽  
...  
Keyword(s):  
Stem Cells ◽  
Leukemic Cell ◽  
Leukemia Stem Cells ◽  
P Value ◽  
Healthy Controls ◽  
Functional Studies ◽  
Cxcr2 Expression ◽  
Cd34 Cells

Abstract Acute Myeloid Leukemia (AML) and Myelodysplastic syndrome (MDS) arise from accumulation of multiple stepwise genetic and epigenetic changes in hematopoietic stem cells (HSC) and/or committed progenitors. A series of transforming events can initially give rise to pre-leukemia stem cells (pre-LSC) as well as fully transformed leukemia stem cells (LSC), both of which need to be targeted in strategies aimed at curing these diseases. We conducted parallel transcriptional analysis of multiple, highly fractionated stem and progenitor populations in individual patients of MDS and AML (N=16) and identified candidate genes that are consistently dysregulated at multiple immature stem and progenitor cell stages. Interleukin 8 (IL8), was one of the most consistently overexpressed genes in MDS/AML Hematolpoetic Stem Cells (HSCs) and progenitors when compared to healthy control HSCs and progenitors. IL8 is a pro-inflammatory chemokine, which is able to activate multiple intracellular signaling pathways after binding to its surface receptor CXCR2. Even though increased IL8-CXCR2 signaling has been shown to promote angiogenesis, metastasis and chemotherapy resistance in many solid tumors, its role in AML and MDS is not well elucidated. We further analyzed gene expression profiles of CD34+ cells from 183 MDS patients and found significant increased expression of CXCR2 in MDS when compared to healthy controls (FDR<0.1). Most importantly, analysis of The Cancer Genome Atlas (TCGA) AML (n=200) dataset showed that CXCR2 expression was predictive of significantly adverse prognosis (log rank P value=0.0182; median survival of 245 days in cxcr2 high vs 607 days in cxcr2 low) in patients, further pointing to a critical role of IL8-CXCR2 signaling in AML/MDS. Next, we studied the functional role of IL8 and CXCR2 in AML. A panel of leukemic cell lines (THP-1, U937, KG-1, MOLM13, HL-60, K532) were screened for CXCR2 expression and revealed significantly higher expression when compared to healthy CD34+ control cells. SB-332235, a specific inhibitor of CXCR2 was used for functional studies. CXCR2 inhibition led to significant, (p<0.05) reduction in proliferation in all 6 cell lines tested and an effect was seen as early as 24 hrs of exposure. CXCR2 inhibition was found to lead to G0/G1 cell cycle arrest and trigged apoptosis in THP-1 and U937 cells (p-value 0.004 and 0.02 respectively). Incubation of primary AML/MDS bone marrow samples with SB-332235 similarly lead to significantly reduced proliferation at 24hrs, when compared to healthy CD34+ cells. Selective, and highly significant inhibition of leukemic cell growth was also seen in colony assays from primary MDS/AML samples (mean leukemic colonies in AML/MDS= 73 vs 313 in controls, P < 0.001). Interestingly, inhibition of CXCR2 in primary AML marrow samples led to induction of apoptosis in immature CD34+/CD38- cells when compared to healthy controls. Lastly, xenografting studies with THP-1 leukemic cells revealed that CXCR2 inhibitor treatment led to decreased leukemic burden and organ infiltration when compared to placebo controls in vivo. In summary we have found significantly increased expression of IL8 and its receptor CXCR2 in sorted HSCs and progenitors from AML and MDS patients. High CXCR2 expression was a marker of adverse prognosis in a large cohort of AML patients. Most importantly, in vitro and in vivo functional studies showed that CXCR2 is a potential therapeutic target in AML/MDS and is able to selectively target immature, LSC-enriched cell fractions in AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Regulation of CXCR2 expression and function by a disintegrin and metalloprotease-17 (ADAM17)

2014 ◽  
Vol 97 (3) ◽  
pp. 447-454 ◽  
Author(s):  
Hemant K. Mishra ◽  
Chunmei Long ◽  
Nooshin S. Bahaie ◽  
Bruce Walcheck
Keyword(s):  
Cxcr2 Expression ◽  
And Function

scholarly journals Risk Stratification in Acute Myeloid Leukemia Using CXCR Gene Signatures: A Bioinformatics Analysis

2020 ◽  
Vol 10 ◽  
Author(s):  
Cong Lu ◽  
Jiang Zhu ◽  
Xiangjun Chen ◽  
Yanjie Hu ◽  
Wei Xie ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Chemokine Receptors ◽  
Myeloid Leukemia ◽  
Independent Prognostic Factor ◽  
Cxcr2 Expression ◽  
Relationship Of ◽  
The Relationship ◽  
Acute Myeloid

The role of CXC chemokine receptors in tumors has been an increasingly researched focus in recent years. However, significant prognostic values of CXCR members in acute myeloid leukemia are yet to be explored profoundly. In this study, we firstly made an analysis of the relationship of CXCR family members and AML using samples from TCGA. Our results suggested that transcriptional expressions of CXCRs serve an important role in AML. CXCR transcript expressions, except CXCR1 expression, were significantly increased in AML. It displayed the expression pattern of CXCR members in different AML subtypes according to FAB classification. The correlations of CXCR transcript expression with different genotypes and karyotypes were also present. High CXCR2 expression was found to have a significantly worse prognosis compared with that of low CXCR2 expression, and CXCR2 was also found to be an independent prognostic factor. We also established a CXCR signature to identify high-risk subgroups of patients with AML. It was an independent prognostic factor and could become a powerful method to predict the survival rate of patients.

scholarly journals CXCL1/CXCR2 Paracrine Axis Contributes to Lung Metastasis in Osteosarcoma

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 459 ◽  
Author(s):  
Chia-Chia Chao ◽  
Chiang-Wen Lee ◽  
Tsung-Ming Chang ◽  
Po-Chun Chen ◽  
Ju-Fang Liu
Keyword(s):  
Lung Metastasis ◽  
Molecular Mechanisms ◽  
Lung Metastases ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Cxcr2 Expression ◽  
Metastasis Model ◽  
Human Pulmonary Artery ◽  
Positive Correlations

Osteosarcoma, the most common of all bone malignancies, has a high likelihood of lung metastasis. Up until now, the molecular mechanisms involved in osteosarcomas with lung metastases are not clearly understood. Recent observations have shown that the chemokine CXCL1 and its receptor CXCR2 assist with the homing of neutrophils into the tumor microenvironment. Here, we show that the CXCL1/CXCR2 paracrine axis is crucial for lung metastasis in osteosarcoma. In an in vivo lung metastasis model of osteosarcoma, lung blood vessels expressed CXCL1 and osteosarcoma cells expressed the CXCR2 receptor. CXCR2 expression was higher in osteosarcoma cell lines than in normal osteoblast cells. Immunohistochemistry staining of clinical osteosarcoma specimens revealed positive correlations between CXCR2 expression and pathology stage and also vascular cell adhesion molecule 1 (VCAM-1) expression. High levels of CXCL1 secreted by human pulmonary artery endothelial cells (HPAECs) promoted osteosarcoma cell mobility, which was mediated by the upregulation of VCAM-1 expression. When HPAECs-conditioned media was incubated in osteosarcoma cells, we observed that the CXCR2 receptor and FAK/PI3K/Akt/NF-κB signaling cascade were required for VCAM-1 expression. Our findings illustrate a molecular mechanism of lung metastasis in osteosarcoma and indicate that CXCL1/CXCR2 is worth targeting in treatment schemas.

Expression of the Chemokine Receptor CXCR2 in Normal and Neoplastic Neuroendocrine Cells

2000 ◽  
Vol 124 (4) ◽  
pp. 520-525 ◽  
Author(s):  
Tülay Tecimer ◽  
Jeffrey Dlott ◽  
Anan Chuntharapai ◽  
Alvin W. Martin ◽  
Stephen C. Peiper
Keyword(s):  
Small Bowel ◽  
Immunohistochemical Analysis ◽  
Large Cell ◽  
Small Cell ◽  
Neuroendocrine Cells ◽  
Biologically Active ◽  
Neuroendocrine Neoplasms ◽  
Projection Neurons ◽  
Cxcr2 Expression ◽  
High Level

Abstract Background.—Chemokines effect their proinflammatory and growth regulatory roles through interaction with serpentine receptors. One such receptor, CXCR2, binds multiple CXC chemokines, including interleukin 8, GRO-α, GRO-β, GRO-γ, and NAP-2. We have previously identified CXCR2 expression on myeloid cells, notably mature granulocytes, and projection neurons. Objective.—To determine the expression of CXCR2 by cells of the neuroendocrine system. Design.—Archival specimens from normal neuroendocrine tissues and their malignant counterparts were analyzed by immunohistochemistry with monoclonal antibodies specific for CXCR1 and CXCR2. Results.—Immunohistochemical analysis revealed high-level expression of CXCR2 by cells in the pituitary, adrenal medulla, pancreatic islets, thyroid C cells, scattered Kulchitsky cells in the bronchi, and counterpart neuroendocrine cells in the stomach, small bowel, colon, and appendix. Neuroendocrine neoplasms that demonstrated high-level CXCR2 expression included (1) primary carcinoids localized to the stomach, small bowel, colon, appendix, fallopian tube, ovary, and lung; (2) atypical carcinoids of the lung; (3) metastatic carcinoids; (4) pituitary adenomas; (5) pheochromocytomas; and (6) medullary carcinomas of the thyroid. Small cell lung carcinomas, large cell neuroendocrine carcinomas of the lung, small cell carcinoma of the cervix, Merkel cell carcinomas, neuroblastomas, and malignant melanomas lacked evidence of CXCR2 expression. Conclusions.—The expression of CXCR2 by normal neuroendocrine cells and neoplastic counterparts that have retained phenotypic features of this differentiation program suggests that chemokines may play an important role in functions that are characteristic of this cell type. In addition, this raises the possibility that chemokines may modulate secretion of biologically active products of these cells and their neoplastic counterparts.

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