Abstract
Glioma is the most common form of primary malignant brain cancers. Tumor cell invasiveness is a critical challenge in the clinical management of glioma patients. The invasive biological feature of glioma cell is stimulated by both autocrine and paracrine factors including chemokine IL-8. In this study, we report that the production of IL-8 is higher in glioma tissues and cells than adjacent nontumor tissues (ANT) and normal glial cells. Autocrine IL-8 can increase the invasive ability of glioma cells by binding to CXCR1. In addition, high expression of IL-8 indicates poor prognosis of glioma patients. Furthermore, IL-8 is capable of modulating cell migration and invasion by regulating the activation of RAC1 which resulted in cytoskeletal reorganisation in an ELMO1 dependent manner. Finally, we found that IL-8 could enhance mesenchymal transition(MT) of glioma cells by activating ELMO1-NF-κB-Snail signaling. Our data indicate that IL-8 autocrine is responsible for the invasive phenotype of glioma and IL-8 may be a useful prognostic marker for glioma and novel therapeutic target for glioma invasion intervention.
Keywords:
ANT, adjacent nontumor tissues; CM, conditioned medium; CXCR1, chemokine (C-X-C motif) receptor 1; CXCR2, chemokine (C-X-C motif) receptor 2; Dock180, dedicator of cytokinesis; ELMO1, engulfment and cell motility 1; EMT, epithelial-mesenchymal transition;; ELMO1; IL-8; glioma; invasion.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / chemistry
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Actins / metabolism*
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Adaptor Proteins, Signal Transducing / metabolism*
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Adult
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Aged
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Aged, 80 and over
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Animals
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Autocrine Communication
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Cell Line, Tumor
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Cell Movement / genetics
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Disease Models, Animal
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Disease Progression
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Epithelial-Mesenchymal Transition*
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Female
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Gene Knockdown Techniques
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Glioma / genetics
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Glioma / metabolism*
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Glioma / mortality
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Glioma / pathology*
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Heterografts
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Humans
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Interleukin-8 / genetics
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Interleukin-8 / metabolism*
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Male
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Matrix Metalloproteinase 2 / metabolism
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Matrix Metalloproteinase 9 / metabolism
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Middle Aged
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NF-kappa B / metabolism*
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Neoplasm Grading
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Prognosis
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Protein Binding
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Protein Multimerization
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Receptors, Interleukin-8A / genetics
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Receptors, Interleukin-8A / metabolism
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Snail Family Transcription Factors
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Survival Analysis
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Transcription Factors / metabolism*
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Young Adult
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rac1 GTP-Binding Protein / metabolism
Substances
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Actins
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Adaptor Proteins, Signal Transducing
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ELMO1 protein, human
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Interleukin-8
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NF-kappa B
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Receptors, Interleukin-8A
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Snail Family Transcription Factors
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Transcription Factors
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9
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rac1 GTP-Binding Protein
Grants and funding
This work was supported by National Natural Scientific Foundation of China (81072068, 81472365), Scientific Foundation of Shandong Province(ZR2014HM003, ZR2014HM086, ZR2011HL047), The Young and Middle-Aged Scientists Research Awards Foundation of Shandong Province (2010BSB14050, BS2013YY020), Foundation of Shandong Educational Committee (J14LK13), Shandong medical and health science and technology development plan (2013WS0282) and Foundation of Weifang Scientific Committee (20121230).