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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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorCARNEIRO-LOBO, Tatiana C.
dc.contributor.authorLIMA, Marina T.
dc.contributor.authorMARIANO-OLIVEIRA, Andrea
dc.contributor.authorDUTRA-OLIVEIRA, Angelica
dc.contributor.authorOBA-SHINJO, Sueli M.
dc.contributor.authorMARIE, Suely K. N.
dc.contributor.authorSOGAYAR, Mari C.
dc.contributor.authorMONTEIRO, Robson Q.
dc.date.accessioned2014-09-30T14:42:28Z
dc.date.available2014-09-30T14:42:28Z
dc.date.issued2014
dc.description.abstractThe 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.
dc.description.indexMEDLINE
dc.description.sponsorshipBrazilian National Council for Scientific and Technological Development (CNPq)
dc.description.sponsorshipState of Rio de Janeiro Research Foundation (FAPERJ)
dc.description.sponsorshipState of Sao Paulo Research Foundation (FAPESP)
dc.description.sponsorshipBrazilian Cancer Foundation
dc.identifier.citationONCOLOGY REPORTS, v.31, n.2, p.679-686, 2014
dc.identifier.doi10.3892/or.2013.2880
dc.identifier.eissn1791-2431
dc.identifier.issn1021-335X
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/7548
dc.language.isoeng
dc.publisherSPANDIDOS PUBL LTD
dc.relation.ispartofOncology Reports
dc.rightsrestrictedAccess
dc.rights.holderCopyright SPANDIDOS PUBL LTD
dc.subjectblood coagulation
dc.subjecttissue factor
dc.subjectprotease-activated receptor
dc.subjectvascular endothelial growth factor
dc.subjectinterleukin-8
dc.subjectastrocytoma
dc.subjectglioblastoma
dc.subject.otherhighly procoagulant pattern
dc.subject.othercentral-nervous-system
dc.subject.otherhuman glioma
dc.subject.othertumor angiogenesis
dc.subject.otherblood-coagulation
dc.subject.othercell-lines
dc.subject.othercancer
dc.subject.otherglioblastoma
dc.subject.otherprogression
dc.subject.otherthrombosis
dc.subject.wosOncology
dc.titleExpression of tissue factor signaling pathway elements correlates with the production of vascular endothelial growth factor and interleukin-8 in human astrocytoma patients
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalCARNEIRO-LOBO, Tatiana C.:Univ Fed Rio de Janeiro, Inst Med Biochem, BR-21941590 Rio De Janeiro, Brazil
hcfmusp.author.externalLIMA, Marina T.:Univ Sao Paulo, Cell & Mol Therapy Ctr NUCEL, Inst Chem, Dept Biochem, BR-05508 Sao Paulo, Brazil
hcfmusp.author.externalMARIANO-OLIVEIRA, Andrea:Univ Fed Rio de Janeiro, Inst Med Biochem, BR-21941590 Rio De Janeiro, Brazil
hcfmusp.author.externalDUTRA-OLIVEIRA, Angelica:Univ Fed Rio de Janeiro, Inst Med Biochem, BR-21941590 Rio De Janeiro, Brazil
hcfmusp.author.externalSOGAYAR, Mari C.:Univ Sao Paulo, Cell & Mol Therapy Ctr NUCEL, Inst Chem, Dept Biochem, BR-05508 Sao Paulo, Brazil
hcfmusp.author.externalMONTEIRO, Robson Q.:Univ Fed Rio de Janeiro, Inst Med Biochem, BR-21941590 Rio De Janeiro, Brazil
hcfmusp.citation.scopus27
hcfmusp.contributor.author-fmusphcSUELI MIEKO OBA SHINJO
hcfmusp.contributor.author-fmusphcSUELY KAZUE NAGAHASHI MARIE
hcfmusp.description.beginpage679
hcfmusp.description.endpage686
hcfmusp.description.issue2
hcfmusp.description.volume31
hcfmusp.origemWOS
hcfmusp.origem.pubmed24297570
hcfmusp.origem.scopus2-s2.0-84892415534
hcfmusp.origem.wosWOS:000332694400021
hcfmusp.publisher.cityATHENS
hcfmusp.publisher.countryGREECE
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hcfmusp.remissive.sponsorshipCNPq
hcfmusp.remissive.sponsorshipFAPESP
hcfmusp.remissive.sponsorshipFAPERJ
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