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

Tang, Wei; Li, Zunyan; Li, Xian; Huo, Zhonghua

doi:10.1177/2040620720958586

Cited by 15 publications

(21 citation statements)

References 29 publications

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“…This increase of CXCR2 ligands is also observed for other types of cancers [ 9 , 44 , 45 ]. Moreover, we have recently shown that CXCR2 levels were also increased in human TNBC compared to luminal breast tumors [ 13 ], as shown for other types of cancers [ 46 , 47 , 48 , 49 ]. We find that Cxcr2 ablation leads to an increase of both primary tumor growth and the development of lung metastasis.…”

Section: Discussionmentioning

confidence: 83%

Pivotal Role for Cxcr2 in Regulating Tumor-Associated Neutrophil in Breast Cancer

Timaxian

Vogel

Orcel

et al. 2021

Cancers

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Chemokines present in the tumor microenvironment are essential for the control of tumor progression. We show here that several ligands of the chemokine receptor Cxcr2 were up-regulated in the PyMT (polyoma middle T oncogene) model of breast cancer. Interestingly, the knock-down of Cxcr2 in PyMT animals led to an increased growth of the primary tumor and lung metastasis. The analysis of tumor content of PyMT-Cxcr2−/− animals highlighted an increased infiltration of tumor associated neutrophils (TANs), mirrored by a decreased recruitment of tumor associated macrophages (TAMs) compared to PyMT animals. Analysis of PyMT-Cxcr2−/− TANs revealed that they lost their killing ability compared to PyMT-Cxcr2+/+ TANs. The transcriptomic analysis of PyMT-Cxcr2−/− TANs showed that they had a more pronounced pro-tumor TAN2 profile compared to PyMT TANs. In particular, PyMT-Cxcr2−/− TANs displayed an up-regulation of the pathways involved in reactive oxygen species (ROS) production and angiogenesis and factors favoring metastasis, but reduced apoptosis. In summary, our data reveal that a lack of Cxcr2 provides TANs with pro-tumor effects.

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Section: Discussionmentioning

confidence: 83%

Pivotal Role for Cxcr2 in Regulating Tumor-Associated Neutrophil in Breast Cancer

Timaxian

Vogel

Orcel

et al. 2021

Cancers

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“…CXCR2 has significant pro-tumor functions, where increased CXCR2 expression is associated with poorer patient prognosis, as shown by studies on acute myeloid leukemia [101], invasive ductal breast cancer [102], colorectal cancer [103], esophageal cancer [104], gastric cancer [16,17,105,106], intrahepatic cholangiocellular carcinoma [107], laryngeal squamous cell carcinoma [108], lung adenocarcinoma [109], non-small cell lung cancer [91], ovarian cancer [110,111], pancreatic ductal adenocarcinoma [112]. In contrast, in studies on triplenegative breast cancer [113], colorectal cancer [114], clear cell renal cell carcinoma [115], gastric cancer [116] and pancreatic ductal adenocarcinoma [117] (Table 1), no such association is shown, which may be related to the initiation of an antitumor immune response resulting in tumor infiltration by tumor-infiltrating lymphocytes (TILs), in particular CD8 + cytotoxic lymphocytes [113].…”

Section: The Role Of Cxcr2 In Cancermentioning

confidence: 97%

CXCR2 Receptor: Regulation of Expression, Signal Transduction, and Involvement in Cancer

Korbecki

Kupnicka

Chlubek

et al. 2022

IJMS

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Chemokines are a group of about 50 chemotactic cytokines crucial for the migration of immune system cells and tumor cells, as well as for metastasis. One of the 20 chemokine receptors identified to date is CXCR2, a G-protein-coupled receptor (GPCR) whose most known ligands are CXCL8 (IL-8) and CXCL1 (GRO-α). In this article we present a comprehensive review of literature concerning the role of CXCR2 in cancer. We start with regulation of its expression at the transcriptional level and how this regulation involves microRNAs. We show the mechanism of CXCR2 signal transduction, in particular the action of heterotrimeric G proteins, phosphorylation, internalization, intracellular trafficking, sequestration, recycling, and degradation of CXCR2. We discuss in detail the mechanism of the effects of activated CXCR2 on the actin cytoskeleton. Finally, we describe the involvement of CXCR2 in cancer. We focused on the importance of CXCR2 in tumor processes such as proliferation, migration, and invasion of tumor cells as well as the effects of CXCR2 activation on angiogenesis, lymphangiogenesis, and cellular senescence. We also discuss the importance of CXCR2 in cell recruitment to the tumor niche including tumor-associated neutrophils (TAN), tumor-associated macrophages (TAM), myeloid-derived suppressor cells (MDSC), and regulatory T (Treg) cells.

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“…To identify potential major regulators along with their subgroup-specific expression behavior, we learned gene regulatory networks associated with the observed expression changes between the three T-PLL subgroups ( Fig 6 ). Most of the 41 revealed genes with increased network connectivity have been reported to be involved in different types of cancer and several of them have been shown to be important in different types of leukemia ( Table 1 , ALPP [ 34 ], AHSP [ 44 ], CXCL8 [ 37 ], CXCR2 [ 47 ], ELANE [ 53 ], FFAR2 [ 40 ], G0S2 [ 38 ], GIMAP2 [ 55 ], IL1RN [ 39 ], LCN2 [ 36 ], MBTD1 [ 51 ], PPP1R15A [ 49 ]). Thus, it is likely that at least some of these genes may also contribute to T-PLL development and that their subgroup-specific expression behavior may contribute to the globally observed gene expression differences of the T-PLL subgroups.…”

Section: Discussionmentioning

confidence: 99%

Computational gene expression analysis reveals distinct molecular subgroups of T-cell prolymphocytic leukemia

et al. 2022

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T-cell prolymphocytic leukemia (T-PLL) is a rare blood cancer with poor prognosis. Overexpression of the proto-oncogene TCL1A and missense mutations of the tumor suppressor ATM are putative main drivers of T-PLL development, but so far only little is known about the existence of T-PLL gene expression subtypes. We performed an in-depth computational reanalysis of 68 gene expression profiles of one of the largest currently existing T-PLL patient cohorts. Hierarchical clustering combined with bootstrapping revealed three robust T-PLL gene expression subgroups. Additional comparative analyses revealed similarities and differences of these subgroups at the level of individual genes, signaling and metabolic pathways, and associated gene regulatory networks. Differences were mainly reflected at the transcriptomic level, whereas gene copy number profiles of the three subgroups were much more similar to each other, except for few characteristic differences like duplications of parts of the chromosomes 7, 8, 14, and 22. At the network level, most of the 41 predicted potential major regulators showed subgroup-specific expression levels that differed at least in comparison to one other subgroup. Functional annotations suggest that these regulators contribute to differences between the subgroups by altering processes like immune responses, angiogenesis, cellular respiration, cell proliferation, apoptosis, or migration. Most of these regulators are known from other cancers and several of them have been reported in relation to leukemia (e.g. AHSP, CXCL8, CXCR2, ELANE, FFAR2, G0S2, GIMAP2, IL1RN, LCN2, MBTD1, PPP1R15A). The existence of the three revealed T-PLL subgroups was further validated by a classification of T-PLL patients from two other smaller cohorts. Overall, our study contributes to an improved stratification of T-PLL and the observed subgroup-specific molecular characteristics could help to develop urgently needed targeted treatment strategies.

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

Cited by 15 publications

References 29 publications

Pivotal Role for Cxcr2 in Regulating Tumor-Associated Neutrophil in Breast Cancer

Pivotal Role for Cxcr2 in Regulating Tumor-Associated Neutrophil in Breast Cancer

CXCR2 Receptor: Regulation of Expression, Signal Transduction, and Involvement in Cancer

Computational gene expression analysis reveals distinct molecular subgroups of T-cell prolymphocytic leukemia

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