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

Tatiana Lobo, Marina T. Lima, Andréa Mariano-Oliveira, Angélica Dutra-Oliveira, Sueli M. Oba-Shinjo, Suely K.N. Marie, Mari C. Sogayar, Robson Q. Monteiro

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)679-686
Number of pages8
JournalOncology Reports
Volume31
Issue number2
DOIs
Publication statusPublished - 1 Feb 2014
Externally publishedYes

Fingerprint

Astrocytoma
Thromboplastin
Interleukin-8
Vascular Endothelial Growth Factor A
Proteinase-Activated Receptors
Glioblastoma
Glioma
Neoplasms
Polymerase Chain Reaction
Blood Coagulation
G-Protein-Coupled Receptors
Peptide Hydrolases
Immunohistochemistry
Cell Line
Peptides
Therapeutics

Keywords

  • Astrocytoma
  • Blood coagulation
  • Glioblastoma
  • Interleukin-8
  • Protease-activated receptor
  • Tissue factor
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Expression of tissue factor signaling pathway elements correlates with the production of vascular endothelial growth factor and interleukin-8 in human astrocytoma patients. / Lobo, Tatiana; Lima, Marina T.; Mariano-Oliveira, Andréa; Dutra-Oliveira, Angélica; Oba-Shinjo, Sueli M.; Marie, Suely K.N.; Sogayar, Mari C.; Monteiro, Robson Q.

In: Oncology Reports, Vol. 31, No. 2, 01.02.2014, p. 679-686.

Research output: Contribution to journalArticle

Lobo, Tatiana ; Lima, Marina T. ; Mariano-Oliveira, Andréa ; Dutra-Oliveira, Angélica ; Oba-Shinjo, Sueli M. ; Marie, Suely K.N. ; Sogayar, Mari C. ; Monteiro, Robson Q. / Expression of tissue factor signaling pathway elements correlates with the production of vascular endothelial growth factor and interleukin-8 in human astrocytoma patients. In: Oncology Reports. 2014 ; Vol. 31, No. 2. pp. 679-686.
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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 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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AU - Oba-Shinjo, Sueli M.

AU - Marie, Suely K.N.

AU - Sogayar, Mari C.

AU - Monteiro, Robson Q.

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