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Article

Expression of tissue factor signaling pathway elements correlates with the production of vascular endothelial growth factor and interleukin-8 in human astrocytoma patients

  • Authors:
    • Tatiana C. Carneiro-Lobo
    • Marina T. Lima
    • Andréa Mariano‑Oliveira
    • Angélica Dutra‑Oliveira
    • Sueli M. Oba-Shinjo
    • Suely K.N. Marie
    • Mari C. Sogayar
    • Robson Q. Monteiro
  • View Affiliations / Copyright

    Affiliations: Institute of Medical Biochemistry, Federal University of Rio de Janeiro, RJ, Brazil, Biochemistry Department, Chemistry Institute, Cell and Molecular Therapy Center (NUCEL), University of São Paulo, SP, Brazil, Department of Neurology, School of Medicine, University of São Paulo, SP, Brazil
  • Pages: 679-686
    |
    Published online on: November 28, 2013
       https://doi.org/10.3892/or.2013.2880
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Abstract

The expression levels of tissue factor (TF), the clotting initiator protein, have been correlated with angiogenesis and the histological grade of malignancy in glioma patients. The pro-tumor function of TF is linked to a family of G protein-coupled receptors known as protease-activated receptors (PARs), which may be activated by blood coagulation proteases. Activation of PARs elicits a number of responses, including the expression of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). In the present study, we analyzed the expression of TF signaling pathway elements (TF, PAR1 and PAR2) and evaluated their correlation with the expression of downstream products (VEGF and IL-8) in human astrocytoma patients. Quantitative PCR (qPCR) showed a significant increase in TF expression in grade IV (glioblastoma) tumors, which was inversely correlated with the expression of the tumor-suppressor PTEN. Immunohistochemistry and qPCR analyses demonstrated a highly significant elevation in the expression of PAR1, but not PAR2, in tumor samples from high-grade astrocytoma patients. The elevated VEGF expression levels detected in the high-grade astrocytoma samples were positively correlated with TF, PAR1 and PAR2 expression. In addition, IL-8 was significantly increased in glioblastoma patients and positively correlated with TF and PAR2 expression. Further in vitro assays employing the human glioma cell lines U87-MG and HOG demonstrated that a synthetic peptide PAR2 agonist stimulated VEGF and IL-8 production. Our findings suggest a role for TF signaling pathway elements in astrocytoma progression, particularly in glioblastoma. Therefore, TF/PAR signaling elements may be suitable targets for the development of new therapies for the treatment of aggressive glioma.
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Copy and paste a formatted citation
Spandidos Publications style
Carneiro-Lobo TC, Lima MT, Mariano‑Oliveira A, Dutra‑Oliveira A, Oba-Shinjo SM, Marie SK, Sogayar MC and Monteiro RQ: Expression of tissue factor signaling pathway elements correlates with the production of vascular endothelial growth factor and interleukin-8 in human astrocytoma patients. Oncol Rep 31: 679-686, 2014.
APA
Carneiro-Lobo, T.C., Lima, M.T., Mariano‑Oliveira, A., Dutra‑Oliveira, A., Oba-Shinjo, S.M., Marie, S.K. ... Monteiro, R.Q. (2014). Expression of tissue factor signaling pathway elements correlates with the production of vascular endothelial growth factor and interleukin-8 in human astrocytoma patients. Oncology Reports, 31, 679-686. https://doi.org/10.3892/or.2013.2880
MLA
Carneiro-Lobo, T. C., Lima, M. T., Mariano‑Oliveira, A., Dutra‑Oliveira, A., Oba-Shinjo, S. M., Marie, S. K., Sogayar, M. C., Monteiro, R. Q."Expression of tissue factor signaling pathway elements correlates with the production of vascular endothelial growth factor and interleukin-8 in human astrocytoma patients". Oncology Reports 31.2 (2014): 679-686.
Chicago
Carneiro-Lobo, T. C., Lima, M. T., Mariano‑Oliveira, A., Dutra‑Oliveira, A., Oba-Shinjo, S. M., Marie, S. K., Sogayar, M. C., Monteiro, R. Q."Expression of tissue factor signaling pathway elements correlates with the production of vascular endothelial growth factor and interleukin-8 in human astrocytoma patients". Oncology Reports 31, no. 2 (2014): 679-686. https://doi.org/10.3892/or.2013.2880
Copy and paste a formatted citation
x
Spandidos Publications style
Carneiro-Lobo TC, Lima MT, Mariano‑Oliveira A, Dutra‑Oliveira A, Oba-Shinjo SM, Marie SK, Sogayar MC and Monteiro RQ: Expression of tissue factor signaling pathway elements correlates with the production of vascular endothelial growth factor and interleukin-8 in human astrocytoma patients. Oncol Rep 31: 679-686, 2014.
APA
Carneiro-Lobo, T.C., Lima, M.T., Mariano‑Oliveira, A., Dutra‑Oliveira, A., Oba-Shinjo, S.M., Marie, S.K. ... Monteiro, R.Q. (2014). Expression of tissue factor signaling pathway elements correlates with the production of vascular endothelial growth factor and interleukin-8 in human astrocytoma patients. Oncology Reports, 31, 679-686. https://doi.org/10.3892/or.2013.2880
MLA
Carneiro-Lobo, T. C., Lima, M. T., Mariano‑Oliveira, A., Dutra‑Oliveira, A., Oba-Shinjo, S. M., Marie, S. K., Sogayar, M. C., Monteiro, R. Q."Expression of tissue factor signaling pathway elements correlates with the production of vascular endothelial growth factor and interleukin-8 in human astrocytoma patients". Oncology Reports 31.2 (2014): 679-686.
Chicago
Carneiro-Lobo, T. C., Lima, M. T., Mariano‑Oliveira, A., Dutra‑Oliveira, A., Oba-Shinjo, S. M., Marie, S. K., Sogayar, M. C., Monteiro, R. Q."Expression of tissue factor signaling pathway elements correlates with the production of vascular endothelial growth factor and interleukin-8 in human astrocytoma patients". Oncology Reports 31, no. 2 (2014): 679-686. https://doi.org/10.3892/or.2013.2880
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