The emerging role of chemokine receptor CXCR2 in cancer progression

Jaffer, Tanweer; Ma, Ding

doi:10.21037/tcr.2016.10.06

Cited by 41 publications

(30 citation statements)

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“…CXCL1 was the most upregulated protein in the supernatants of inflamed compared to unstimulated BM-MSC; on the other hand, pre-leukemic Ba/F3 and patient-derived E/R + blasts overexpress its receptor CXCR2. Although CXCR2 does not directly favor the emergence of pre-leukemic cells within the inflamed mesenchymal niche, it is responsible for the preferential migration of E/R-expressing cells toward the sustaining niche, thus becoming a possible future therapeutic target (Ijichi et al, 2011;Martz, 2012;Schinke et al, 2015;Jaffer & Ma, 2016).…”

Section: Discussionmentioning

confidence: 99%

Pro‐inflammatory cytokines favor the emergence of ETV6‐RUNX1‐positive pre‐leukemic cells in a model of mesenchymal niche

et al. 2020

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ETV6-RUNX1 (E/R) fusion gene, arising in utero from translocation t(12;21)(p13:q22), is the most frequent alteration in childhood acute lymphoblastic leukemia (ALL). However, E/R is insufficient to cause overt leukemia since it generates a clinically silent pre-leukemic clone which persists in the bone marrow but fails to out-compete normal progenitors. Conversely, pre-leukemic cells show increased susceptibility to transformation following additional genetic insults. Infections/inflammation are the most accredited triggers for mutations accumulation and leukemic transformation in E/R + pre-leukemic cells. However, precisely how E/R and inflammation interact in promoting leukemia is still poorly understood. Here we demonstrate that IL6/TNFa/ILb pro-inflammatory cytokines cooperate with BM-MSC in promoting the emergence of E/R + Ba/F3 over their normal counterparts by differentially affecting their proliferation and survival. Moreover, IL6/TNFa/ILb-stimulated BM-MSC strongly attract E/R + Ba/F3 in a CXCR2-dependent manner. Interestingly, E/R-expressing human CD34 + IL7R + progenitors, a putative population for leukemia initiation during development, were preserved in the presence of BM-MSC and IL6/ TNFa/ILb compared to their normal counterparts. Finally, the extent of DNA damage increases within the inflamed niche in both control and E/Rexpressing Ba/F3, potentially leading to transformation in the apoptosis-resistant pre-leukemic clone. Overall, our data provide new mechanistic insights into childhood ALL pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Pro‐inflammatory cytokines favor the emergence of ETV6‐RUNX1‐positive pre‐leukemic cells in a model of mesenchymal niche

et al. 2020

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“…Treatment with γ-T downregulated CXCR2 gene expression. CXCR2 has been associated with poor outcomes for different cancers through its effects on migration, invasion and angiogenesis (36). In breast cancer, targeting CXCR2 has been reported to enhance chemotherapeutic response and inhibit tumor growth, angiogenesis and lung metastasis in vivo (37).…”

Section: Discussionmentioning

confidence: 99%

Differential Gene Regulation and Tumor-Inhibitory Activities of Alpha-, Delta-, and Gamma-Tocopherols in Estrogen-Mediated Mammary Carcinogenesis

Gupta

Patel

Wahler

et al. 2017

Cancer Prevention Research

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Despite experimental evidence elucidating the anti-tumor activities of tocopherols, clinical trials with α-tocopherol (α-T) have failed to demonstrate its beneficial effects in cancer prevention. This study compared the chemopreventive efficacy of individual tocopherols (α-, δ-, γ-T) and a γ-T rich tocopherol mixture (γ-TmT) in the August Copenhagen Irish (ACI) rat model of estrogen-mediated mammary cancer. Female ACI rats receiving 17β-estradiol (E2) implants were administered with 0.2% α-T, δ-T, γ-T or γ-TmT for 30 weeks. While α-T had no significant effects on mammary tumor growth in ACI rats, δ-T, γ-T and γ-TmT reduced mammary tumor volume by 51% (p < 0.05), 60% (p < 0.01) and 59% (p < 0.01), respectively. Immunohistochemical analysis revealed that δ-T, γ-T and γ-TmT reduced levels of the cell proliferation marker, PCNA, in the rat mammary tumors. To gain further insight into the biological functions of different forms of tocopherols, RNA-seq analysis of the tumors was performed. Treatment with γ-T induced robust gene expression changes in the mammary tumors of ACI rats. IPA analysis identified ‘Cancer’ as a top disease pathway and ‘Tumor growth’ and ‘Metastasis’ as the top signaling pathways modulated by γ-T. Although the results need further functional validation, this study presents an unbiased attempt to understand the differences between biological activities of individual forms of tocopherols at the whole transcriptome level. δ-T, γ-T and γ-TmT could be promising agents for the prevention of estrogen-mediated mammary carcinogenesis. γ-T suppressed growth of mammary tumors most effectively in ACI rats.

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“…Chemokines are a group of low-molecular-weight chemotactic cytokines that participate in various cellular processes such as embryogenesis, angiogenic activity, leukocyte migration and tumor growth and metastasis [11][12][13]. CXCLs/CXCR2 signaling is important in both cancer and different inflammatory diseases.…”

Section: Introductionmentioning

confidence: 99%

“…CXCLs/CXCR2 signaling is important in both cancer and different inflammatory diseases. Because the increased expression of CXCR2 and neutrophil/monocyte migration is critical in chronic inflammation and cancer, the need to focus on using CXCR2 antagonists in cancer and related diseases drugs development remains eminent [12,13]. CXCL1 gene as well as its receptor CXCR2 gene have been found to be highly associated with tumorigenesis, angiogenesis, and metastasis [11,12].…”

Section: Introductionmentioning

confidence: 99%

Annona muricata silver nanoparticles exhibit strong anticancer activities against cervical and prostate adenocarcinomas through regulation of CASP9 and the CXCL1/CXCR2 genes axis

Gavamukulya

Maina

El‐Shemy

et al. 2021

TUB

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BACKGROUND: Green synthesized nanoparticles have been earmarked for use in nanomedicine including for the development of better anticancer drugs. OBJECTIVE: The aim of this study was to undertake biochemical evaluation of anticancer activities of green synthesized silver nanoparticles (AgNPs) from ethanolic extracts of fruits (AgNPs-F) and leaves (AgNPs-L) of Annona muricata. METHODS: Previously synthesized silver nanoparticles were used for the study. The effects of the AgNPs and 5-Fluorouracil were studied on PC3, HeLa and PNT1A cells. The resazurin, migration and colonogenic assays as well as qRT-PCR were employed. RESULTS: The AgNPs-F displayed significant antiproliferative effects against HeLa cells with an IC50 of 38.58μg/ml and PC3 cells with an IC50 of 48.17μg/ml but selectively spared normal PNT1A cells (selectivity index of 7.8), in comparison with first line drug 5FU and AgNPs-L whose selectivity index were 3.56 and 2.26 respectively. The migration assay revealed potential inhibition of the metastatic activity of the cells by the AgNPs-F while the colonogenic assay indicated the permanent effect of the AgNPs-F on the cancer cells yet being reversible on the normal cells in contrast with 5FU and AgNPs-L. CASP9 was significantly over expressed in all HeLa cells treated with the AgNPs-F (1.53-fold), AgNPs-L (1.52-fold) and 5FU (4.30-fold). CXCL1 was under expressed in HeLa cells treated with AgNPs-F (0.69-fold) and AgNPs-L (0.58-fold) and over expressed in cells treated with 5FU (4.95-fold), but the difference was not statistically significant. CXCR2 was significantly over expressed in HeLa cells treated with 5FU (8.66-fold) and AgNPs-F (1.12-fold) but under expressed in cells treated with AgNPs-L (0.76-fold). CONCLUSIONS: Here we show that biosynthesized AgNPs especially AgNPs-F can be used in the development of novel and better anticancer drugs. The mechanism of action of the AgNPs involves activation of the intrinsic apoptosis pathway through upregulation of CASP9 and concerted down regulation of the CXCL1/ CXCR2 gene axis.

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The emerging role of chemokine receptor CXCR2 in cancer progression

Cited by 41 publications

References 0 publications

Pro‐inflammatory cytokines favor the emergence of ETV6‐RUNX1‐positive pre‐leukemic cells in a model of mesenchymal niche

Pro‐inflammatory cytokines favor the emergence of ETV6‐RUNX1‐positive pre‐leukemic cells in a model of mesenchymal niche

Differential Gene Regulation and Tumor-Inhibitory Activities of Alpha-, Delta-, and Gamma-Tocopherols in Estrogen-Mediated Mammary Carcinogenesis

Annona muricata silver nanoparticles exhibit strong anticancer activities against cervical and prostate adenocarcinomas through regulation of CASP9 and the CXCL1/CXCR2 genes axis

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