Role of MIF/CXCL8/CXCR2 signaling in the growth of nasopharyngeal carcinoma tumor spheres

Lo, Ming Chu; Yip, Tak Chun; Ngan, K.C.; Cheng, Wai Wai; Law, C.K.; Chan, Ping Shing; Chan, King Chi; Wong, Chris K C; Wong, Ricky N S; Lo, Kwok Wai; Ng, Wai Tong; Lee, Wing Mui; Tsao, Sai Wah; Kwong, Lai Wan Dora; Lung, Maria Li; Mak, Nai Ki

doi:10.1016/j.canlet.2013.01.052

Cited by 47 publications

(36 citation statements)

References 44 publications

(37 reference statements)

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“…Blocking of IL 8 receptors using SB225002 was able to abrogate the IL 8-driven LAMA84 cell survival and phosphorylation of AKT in vitro as well as the growth of CML xenograft in vivo thus indicating a key role of CXCL8/CXCR1-2/AKT signalling for the growth of CML cells. Similar results, obtained by Hinohara et al and by Ming-Chu et al, demonstrated the involvement of CXCL8 and activation of AKT-dependent signalling pathways in breast cancer and nasopharyngeal tumour growth respectively [26,27].…”

Section: Discussionsupporting

confidence: 78%

Exosome-mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an Interleukin 8-dependent survival of leukemia cells

Corrado¹,

Raimondo²,

Saieva³

et al. 2014

Cancer Letters

155

134

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a b s t r a c tChronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by the Bcr-Abl oncoprotein with constitutive tyrosine kinase activity. Exosomes are nanovesicles released by cancer cells that are involved in cell-to-cell communication thus potentially affecting cancer progression. It is well known that bone marrow stromal microenvironment contributes to disease progression through the establishment of a bi-directional crosstalk with cancer cells. Our hypothesis is that exosomes could have a functional role in this crosstalk. Interleukin-8 (IL 8) is a proinflammatory chemokine that activates multiple signalling pathways downstream of two receptors (CXCR1 and CXCR2). We demonstrated that exosomes released from CML cells stimulate bone marrow stromal cells to produce IL 8 that, in turn, is able to modulate both in vitro and in vivo the leukemia cell malignant phenotype.

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Section: Discussionsupporting

confidence: 78%

Exosome-mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an Interleukin 8-dependent survival of leukemia cells

Corrado¹,

Raimondo²,

Saieva³

et al. 2014

Cancer Letters

155

134

View full text Add to dashboard Cite

show abstract

“…This initial, impactful finding showed that MIF induced cell proliferation through the MAP kinase cascade. Continuing studies suggested that CD74 couples with CXCR2 or CXCR4 to induce signaling events [18], [35]. Further studies also found a role for the Akt pathway in general cell survival studies [36], [37].…”

Section: Discussionmentioning

confidence: 90%

Chronic Macrophage Migration Inhibitory Factor Exposure Induces Mesenchymal Epithelial Transition and Promotes Gastric and Colon Cancers

et al. 2014

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Macrophage Migration Inhibitory Factor (MIF) is an inflammatory cytokine that is highly produced in gastrointestinal cancers. Since chronic inflammation is a risk factor for tumorigenesis in these cancers, in this study, the role of MIF in pro-tumorigenic events was examined. MIF and its receptor, CD74, were examined in gastric and colon tumors and found to be increased in most tumors with significantly higher expression in tumors from patients with lymph node metastasis. MIF was also found to be highly produced by cancer associated fibroblasts isolated from human tumors compared to fibroblasts from matched normal tissues from uninvolved areas. Fibroblast-produced MIF highly increased GI cancer cell proliferation, which was decreased upon neutralizing MIF or CD74. Chronic MIF treatment led to sustained proliferation and signaling events in non-transformed GI fibroblast cells, which was maintained upon removing MIF treatment for 8 weeks. Additionally, chronic treatment of normal GI cells expressing fibroblast markers for up to 16 weeks with MIF led to a drastic decrease of fibroblast markers with concurrent increase of epithelial markers. Transformation was examined by telomerase and focus forming assays. These results suggest the MIF promotes mesenchymal epithelial transition, cell transformation and tumorigenesis in GI cancers, and thus may be an important link between chronic inflammation and tumorigenesis.

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“…Previous studies have shown that IL8 promotes tumor angiogenesis, growth, and metastasis in the various types of cancers, including NPC (25)(26)(27)(28)(29)(30)(31). Increased serum and tissue IL8 levels are associated with worse prognosis of NPC patients, and can serve as an independent prognostic factor for overall patient survival (31,32).…”

Section: Introductionmentioning

confidence: 99%

MiRNA-203 Reduces Nasopharyngeal Carcinoma Radioresistance by Targeting IL8/AKT Signaling

et al. 2015

Molecular Cancer Therapeutics

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Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment, but little is known about how miRNA (miR) regulates this phenomenon. In this study, we investigated the function and mechanism of miR-203 in NPC radioresistance, one of downregulated miRs in the radioresistant NPC cells identified by our previous microarray analysis. We observed that miR-203 was frequently downregulated in the radioresistant NPC tissues compared with radiosensitive NPC tissues, and its decrement significantly correlated with NPC radioresistance and poor patient survival, and was an independent predictor for reduced patient survival. In vitro radioresponse assays showed that miR-203 mimic markedly decreased NPC cell radioresistance. In a mouse model, therapeutic administration of miR-203 agomir dramatically sensitized NPC xenografts to irradiation. Mechanistically, we confirmed that IL8 was a direct target of miR-203, and found that reduced miR-203 promoted NPC cell radioresistance by activating IL8/ AKT signaling. Moreover, the levels of IL8 and phospho-AKT were significantly increased in the radioresistant NPC tissues compared with radiosensitive NPC tissues, and negatively associated with miR-203 level. Our data demonstrate that miR-203 is a critical determinant of NPC radioresponse, and its decrement enhances NPC radioresistance through targeting IL8/AKT signaling, highlighting the therapeutic potential of the miR-203/IL8/AKT signaling axis in NPC radiosensitization. Mol Cancer Ther; 14(11); 2653-64. Ó2015 AACR.

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Role of MIF/CXCL8/CXCR2 signaling in the growth of nasopharyngeal carcinoma tumor spheres

Cited by 47 publications

References 44 publications

Exosome-mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an Interleukin 8-dependent survival of leukemia cells

Exosome-mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an Interleukin 8-dependent survival of leukemia cells

Chronic Macrophage Migration Inhibitory Factor Exposure Induces Mesenchymal Epithelial Transition and Promotes Gastric and Colon Cancers

MiRNA-203 Reduces Nasopharyngeal Carcinoma Radioresistance by Targeting IL8/AKT Signaling

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