Functional activity of CXCL8 receptors, CXCR1 and CXCR2, on human malignant melanoma progression

Gabellini, Chiara; Trisciuoglio, Daniela; Desideri, Marianna; Candiloro, Antonio; Ragazzoni, Ylenia; Orlandi, Augusto; Zupi, Gabriella; Bufalo, Donatella Del

doi:10.1016/j.ejca.2009.07.007

Cited by 122 publications

(89 citation statements)

References 33 publications

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“…Chemokines, including CXCL8, can modulate adhesion, invasion and migration of a variety of tumor cells, such as prostate cancer cells (Li et al 2005;Gabellini et al 2009;Singh et al 2011). Our current study further confirmed these data.…”

Section: Discussionsupporting

confidence: 86%

G31P, an Antagonist against CXC Chemokine Receptors 1 and 2, Inhibits Growth of Human Prostate Cancer Cells in Nude Mice

Liu

Peng

Sun

et al. 2012

Tohoku J. Exp. Med.

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Section: Discussionsupporting

confidence: 86%

G31P, an Antagonist against CXC Chemokine Receptors 1 and 2, Inhibits Growth of Human Prostate Cancer Cells in Nude Mice

Liu

Peng

Sun

et al. 2012

Tohoku J. Exp. Med.

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“…The fact that occasional pseudopalisading cells expressed CXCR2 and that CXCR2 expression correlated with the extent of necrosis indicates that hypoxia is one of the mechanisms upregulating CXCR2. Indeed, experimental data support this notion indicating the presence of hypoxia-response elements in the CXCR2 promoter (24). CXCR2 expression was recorded in approximately half of our cases, usually at low levels, as reported by Zhou et al (22), and was higher in glioblastomas compared with astrocytomas and anaplastic astrocytomas.…”

Section: Discussionsupporting

confidence: 72%

“…A similar autocrine signaling between IL-1 and CXCR2 was suggested to operate in early-stage colorectal cancer (26). Upregulation of CXCR2 mediates IL-8-induced invasive and migratory phenotype of melanoma cells (24) and is associated with a more aggressive phenotype in hepatocellular (27), gastric (28) and colorectal (29) carcinoma. The mechanisms by which CXCR2 facilitates transformation and migratory responses evoked during oncogenesis are, at least partially, due to manipulation of a comprehensive signaling network comprising phosphati dylinositol 3-kinase/protein kinase B (AKT), nuclear factor κB, Ras, mitogen-activated protein kinase (MAPK) and JAK/STAT-3 (28,(30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Expression of Interleukin-8 Receptor CXCR2 and Suppressor of Cytokine Signaling-3 in Astrocytic Tumors

Korkolopoulou

Levidou

El-Habr

et al. 2012

Mol Med

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The aim was to expand recently published information regarding the significance of the interleukin (IL)-8/p-STAT-3 (signal transducer and activator of transcription) pathway in astrocytomas, focusing on the IL-8 receptor, chemokine (C-X-C motif) receptor 2 (CXCR2), and the STAT-3 inhibitor SOCS-3 (suppressors of cytokine signaling). A total of 91 paraffin-embedded human astrocytoma tissues (grades II-IV) were investigated for the association of SOCS-3 and CXCR2 expression with clinicopathologic and morphometric microvascular characteristics, vascular endothelial growth factor (VEGF), IL-8 and p-STAT-3 expression and patient survival. Peripheral IL-8 secretion levels were assessed by enzyme-linked immunosorbent spot (ELISPOT). SOCS-3, p-STAT-3 and CXCR2 protein levels were also quantified by Western immunoblotting in six cases, and the protein levels of SOCS-3 and CXCR2 were correlated with the immunohistochemical expression of the respective proteins. All CXCR2-positive cases by Western immunoblotting displayed increased peripheral IL-8 secretion levels. Treatment of primary glioblastoma cell cultures with exogenous IL-8 enhanced proliferation, and this effect was inhibited by treatment with a neutralizing anti-CXCR2 antibody. SOCS-3 and CXCR2 were expressed by neoplastic astrocytes in 92.4% and 48.78% of cases, respectively, with their levels increasing with histological grade and extent of necrosis. VEGF expression and microvessel density, CXCR2 and IL-8 levels were interrelated. SOCS-3 and p-STAT-3 were coexpressed in 85.7% of cases, although they were not interrelated. In univariate survival analysis, increased SOCS-3 expression and the presence of CXCR2 adversely affected survival, whereas in multivariate analysis, only CXCR2 remained significant. The prognostic significance of CXCR2 was validated in an independent set of 63 patients. Our data implicate IL-8/CXCR2 signaling pathway in the progression and regulation of angiogenesis in astrocytomas and provide a rationale for CXCR2 therapeutic exploitation in these tumors.

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“…CXCL8-driven chemotaxis can be elicited in many cell types expressing CXCR1/2. It has an important role in fibroblast-mediated wound healing 37 , the formation of tumour metastases 38 , and neutrophile chemotaxis 37 . Chemotaxis forms and dismantles focal complexes and adhesions, and dynamically modulates anchorage of cells to the extracellular matrix.…”

Section: Discussionmentioning

confidence: 99%

Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells

et al. 2011

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mucosal epithelia provide strong barriers against pathogens. For instance, the outward facing apical membrane of polarized epithelial cells lacks receptors for agents, such as hepatitis C virus, herpesvirus, reovirus, poliovirus or adenovirus. In addition, macrophages eliminate pathogens from the luminal space. Here we show that human adenovirus type 5 engages an antiviral immune response to enter polarized epithelial cells. Blood-derived macrophages co-cultured apically on polarized epithelial cells facilitate epithelial infection. Infection also occurs in the absence of macrophages, if virus-conditioned macrophage-medium containing the chemotactic cytokine CXCL8 (interleukin-8), or recombinant CXCL8 are present. In polarized cells, CXCL8 activates a src-family tyrosine kinase via the apical CXCR1 and CXCR2 receptors. This activation process relocates the viral co-receptor ανβ3 integrin to the apical surface, and enables apical binding and infection with adenovirus depending on the primary adenovirus receptor CAR. This paradigm may explain how other mucosal pathogens enter epithelial cells.

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Functional activity of CXCL8 receptors, CXCR1 and CXCR2, on human malignant melanoma progression

Cited by 122 publications

References 33 publications

G31P, an Antagonist against CXC Chemokine Receptors 1 and 2, Inhibits Growth of Human Prostate Cancer Cells in Nude Mice

G31P, an Antagonist against CXC Chemokine Receptors 1 and 2, Inhibits Growth of Human Prostate Cancer Cells in Nude Mice

Expression of Interleukin-8 Receptor CXCR2 and Suppressor of Cytokine Signaling-3 in Astrocytic Tumors

Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells

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