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

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Arquivos
art_CARNEIRO-LOBO_Expression_of_tissue_factor_signaling_pathway_elements_correlates_2014.PDF (565.27 KB)
Citações na Scopus
27
Tipo de produção
article
Data de publicação
2014
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
SPANDIDOS PUBL LTD
Autores
CARNEIRO-LOBO, Tatiana C.
LIMA, Marina T.
MARIANO-OLIVEIRA, Andrea
DUTRA-OLIVEIRA, Angelica
SOGAYAR, Mari C.
MONTEIRO, Robson Q.
Citação
ONCOLOGY REPORTS, v.31, n.2, p.679-686, 2014
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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.
Palavras-chave
blood coagulation, tissue factor, protease-activated receptor, vascular endothelial growth factor, interleukin-8, astrocytoma, glioblastoma
URI
https://observatorio.fm.usp.br/handle/OPI/7548
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MNE
Artigos e Materiais de Revistas Científicas - LIM/15
Artigos e Materiais de Revistas Científicas - ODS/03