The role of CXC chemokines in the transition of chronic inflammation to esophageal and gastric cancer

Verbeke, Hannelien; Geboes, Karel; Damme, Jozef Van; Struyf, Sofie

doi:10.1016/j.bbcan.2011.10.008

Cited by 79 publications

(62 citation statements)

References 176 publications

(268 reference statements)

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“…[110][111][112] Infiltrating neutrophils have also been shown to contribute to the pool of IL8 thereby facilitating the progression of BE and EAC. 113 Nguyen et al in their study demonstrated a relation between increased IL8 expression and poorer prognosis in esophageal cancer confirming the pro-tumoral role of IL8. 114 Thus our previous work and these studies promoted us to further examine the effect of IL8 pathway inhibition in esophageal cancer.…”

Section: Reflux Disease Barrett's Esophagus (Be) and Esophageal Adenmentioning

confidence: 82%

Targeting chemokine pathways in esophageal adenocarcinoma

et al. 2014

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y These authors Contributed equally to this work. E sophageal adenocarcinoma (EAC) is one of the fastest growing malignancies in the US and needs newer therapeutic and diagnostic strategies. Chronic inflammation plays a role in the pathogenesis of EAC and contributes to the dysplastic conversion of normal esophageal epithelium to Barrett's esophagus and frank adenocarcinoma. Chemokines play important roles in mediating inflammation and recent evidence implicates these ligands and their receptors in the development and spread of various tumors. We demonstrated that the chemokines IL8, CXCL1 and CXCL3 are significantly overexpressed during esophageal carcinogenesis and accompanied by amplification and demethylation of the chr4q21 gene locus. We also demonstrated that IL8 levels can be detected in serum of patients with EAC and can serve as potential biomarkers. We now demonstrate that inhibition of IL8 receptor, CXCR2, leads to decreased invasiveness of esophageal adenocarcinoma derived cells without affecting cellular proliferation. Taken together, these studies reveal the important roles that chemokines play in development of esophageal cancer and demonstrate that these pathways can serve as potential therapeutic targets.

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Section: Reflux Disease Barrett's Esophagus (Be) and Esophageal Adenmentioning

confidence: 82%

Targeting chemokine pathways in esophageal adenocarcinoma

et al. 2014

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“…Some chemokines promote conditions favorable for tumor growth and progression, while others have antitumor activity [252]. For example, IL8/CXCL8 induces leukocyte cell migration during inflammation, and this response can promote tumor growth and development by generating a favorable microenvironment [252, 253]. …”

Section: Therapeutic Targetsmentioning

confidence: 99%

A multi-targeted approach to suppress tumor-promoting inflammation

Samadi

Bilsland

Georgakilas

et al. 2015

Seminars in Cancer Biology

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Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-kappaB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes.

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“…Previous studies, utilizing the zebrafish model system, have shown that Cxcr2 receptor signaling axis is involved in both long-range systemic neutrophil mobilization from hematopoietic tissue as well as local recruitment to infection or purified Cxcl8 (IL-8, a potent Cxcr2 ligand) [17], [18]. Previous studies have also implicated CXCR2 signaling in tumor progression [21], [22], [24]–[29]. CXCR2 expression is increased in some tumor types [26], [30]–[32] and pharmacological inhibition of CXCR1 and CXCR2 inhibits neutrophil recruitment into A547 lung tumor spheroids resulting in slower tumor growth [33].…”

Section: Introductionmentioning

confidence: 99%

Live Imaging and Gene Expression Analysis in Zebrafish Identifies a Link between Neutrophils and Epithelial to Mesenchymal Transition

Freisinger

Huttenlocher

2014

PLoS ONE

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Chronic inflammation is associated with epithelial to mesenchymal transition (EMT) and cancer progression however the relationship between inflammation and EMT remains unclear. Here, we have exploited zebrafish to visualize and quantify the earliest events during epithelial cell transformation induced by oncogenic HRasV12. Live imaging revealed that expression of HRasV12 in the epidermis results in EMT and chronic neutrophil and macrophage infiltration. We have developed an in vivo system to probe and quantify gene expression changes specifically in transformed cells from chimeric zebrafish expressing oncogenic HRasV12 using translating ribosomal affinity purification (TRAP). We found that the expression of genes associated with EMT, including slug, vimentin and mmp9, are enriched in HRasV12 transformed epithelial cells and that this enrichment requires the presence of neutrophils. An early signal induced by HRasV12 in epithelial cells is the expression of il-8 (cxcl8) and we found that the chemokine receptor, Cxcr2, mediates neutrophil but not macrophage recruitment to the transformed cells. Surprisingly, we also found a cell autonomous role for Cxcr2 signaling in transformed cells for both neutrophil recruitment and EMT related gene expression associated with Ras transformation. Taken together, these findings implicate both autocrine and paracrine signaling through Cxcr2 in the regulation of inflammation and gene expression in transformed epithelial cells.

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The role of CXC chemokines in the transition of chronic inflammation to esophageal and gastric cancer

Cited by 79 publications

References 176 publications

Targeting chemokine pathways in esophageal adenocarcinoma

Targeting chemokine pathways in esophageal adenocarcinoma

A multi-targeted approach to suppress tumor-promoting inflammation

Live Imaging and Gene Expression Analysis in Zebrafish Identifies a Link between Neutrophils and Epithelial to Mesenchymal Transition

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