Primary Role for Kinin B-1 and B-2 Receptors in Glioma Proliferation

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dc.citation.issue10
dc.citation.volume54
dc.contributor.authorNicoletti, Natalia Fontana
dc.contributor.authorSenecal, Jacques
dc.contributor.authorda Silva, Vinicius Duval
dc.contributor.authorRoxo, Marcelo R.
dc.contributor.authorFerreira, Nelson Pires
dc.contributor.authorde Morais, Rafael Leite T. [UNIFESP]
dc.contributor.authorPesquero, Joao Bosco [UNIFESP]
dc.contributor.authorCampos, Maria Martha
dc.contributor.authorCouture, Rejean
dc.contributor.authorMorrone, Fernanda Bueno
dc.coverageTotowa
dc.date.accessioned2020-09-01T13:21:13Z
dc.date.available2020-09-01T13:21:13Z
dc.date.issued2017
dc.description.abstractThis study investigated the role of kinins and their receptors in malignant brain tumors. As a first approach, GL-261 glioma cells were injected (2 x 10(5) cells in 2 mu l/2 min) into the right striatum of adult C57/BL6 wild-type, kinin B-1 and B-2 receptor knockout (KOB1R and KOB2R) and B-1 and B-2 receptor double knockout mice (KOB1B2R). The animals received the selective B1R (SSR240612) and/or B2R (HOE-140) antagonists by intracerebroventricular (i.c.v.) route at 5, 10, and 15 days. The tumor size quantification, mitotic index, western blot analysis, quantitative autoradiography, immunofluorescence, and confocal microscopy were carried out in brain tumor samples, 20 days after tumor induction. Our results revealed an uncontrolled tumor growing in KOB1R or SSR240612-treated mice, which was blunted by B2R blockade with HOE-140, suggesting a crosstalk between B1R and B2R in tumor growing. Combined treatment with B1R and B2R antagonists normalized the upregulation of tumor B1R and decreased the tumor size and the mitotic index, as was seen in double KOB1B2R. The B1R was detected on astrocytes in the tumor, indicating a close relationship between this receptor and astroglial cells. Noteworthy, an immunohistochemistry analysis of tumor samples from 16 patients with glioma diagnosis revealed a marked B1R immunopositivity in low-grade gliomas or in older glioblastoma individuals. Furthermore, the clinical data revealed a significantly higher immunopositivity for B1R, when compared to a lower B2R immunolabeling. Taken together, our results show that blocking simultaneously both kinin receptors or alternatively stimulating B1R may be of therapeutic value in the treatment of brain glioblastoma growth and malignancy.en
dc.description.affiliationPontificia Univ Catolica Rio Grande do Sul, Programa Posgrad Biol Celular & Mol, Ave Ipiranga 6681, BR-90619900 Porto Alegre, RS, Brazil
dc.description.affiliationPontificia Univ Catolica Rio Grande do Sul, Inst Toxicol & Farmacol, Ave Ipiranga 6681, BR-90619900 Porto Alegre, RS, Brazil
dc.description.affiliationUniv Montreal, Dept Mol & Integrat Physiol, Fac Med, CP 6128,Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada
dc.description.affiliationPontificia Univ Catolica Rio Grande do Sul, Lab Patol, Hosp Sao Lucas, Ave Ipiranga 6681, BR-90619900 Porto Alegre, RS, Brazil
dc.description.affiliationIrmandade Santa Casa Misericordia Porto Alegre, Hosp Sao Jose, Serv Neurocirurgia, Rua Prof Annes Dias 295, BR-90020090 Porto Alegre, RS, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biofis, Ave Doutor Arnaldo 455, BR-01246903 Sao Paulo, SP, Brazil
dc.description.affiliationPontificia Univ Catolica Rio Grande do Sul, Lab Patol, Fac Odontol, Ave Ipiranga 6681, BR-90619900 Porto Alegre, RS, Brazil
dc.description.affiliationPontificia Univ Catolica Rio Grande do Sul, Fac Farm, Lab Farmacol Aplicada, Ave Ipiranga 6681, BR-90619900 Porto Alegre, RS, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biofis, Ave Doutor Arnaldo 455, BR-01246903 Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFINEP research grant "Implantacao, Modernizacao e Qualificacao de Estrutura de Pesquisa da PUCRS" (PUCRSINFRA)
dc.description.sponsorshipCNPq
dc.description.sponsorshipCAPES
dc.description.sponsorshipFAPERGS
dc.description.sponsorshipCanadian Institutes of Health Research
dc.description.sponsorshipCAPES (AUX-PE/Toxinologia)
dc.description.sponsorshipCAPES/PDSE
dc.description.sponsorshipPROBOLSAS/PUCRS
dc.description.sponsorshipIDFINEP research grant "Implantacao, Modernizacao e Qualificacao de Estrutura de Pesquisa da PUCRS" (PUCRSINFRA): 01.11.0014-00
dc.description.sponsorshipIDCanadian Institutes of Health Research: MOP-119329
dc.format.extent7869-7882
dc.identifierhttp://dx.doi.org/10.1007/s12035-016-0265-9
dc.identifier.citationMolecular Neurobiology. Totowa, v. 54, n. 10, p. 7869-7882, 2017.
dc.identifier.doi10.1007/s12035-016-0265-9
dc.identifier.issn0893-7648
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/58137
dc.identifier.wosWOS:000415341900025
dc.language.isoeng
dc.publisherHumana Press Inc
dc.relation.ispartofMolecular Neurobiology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectGlioblastomaen
dc.subjectKininsen
dc.subjectB1R and B2Ren
dc.titlePrimary Role for Kinin B-1 and B-2 Receptors in Glioma Proliferationen
dc.typeinfo:eu-repo/semantics/article
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