Endostatin gene therapy inhibits intratumoral macrophage M2 polarization

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dc.citation.volume79
dc.contributor.authorFoguer, Karen [UNIFESP]
dc.contributor.authorBraga, Marina de Souza [UNIFESP]
dc.contributor.authorSchatzmann Peron, Jean Pierre
dc.contributor.authorBortoluci, Karina Ramalho [UNIFESP]
dc.contributor.authorBellini, Maria Helena [UNIFESP]
dc.coverageParis
dc.date.accessioned2020-07-22T13:23:17Z
dc.date.available2020-07-22T13:23:17Z
dc.date.issued2016
dc.description.abstractBackground: Renal cell carcinoma (RCC) is a highly vascularized cancer resistant to chemotherapy and radiotherapy. RCC is frequently infiltrated with immune cells, with macrophages being the most abundant cell type. Alternatively activated M2 macrophages are known to contribute to tumor progression. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we investigated the impact of ES gene therapy on the polarization of tumor-associated macrophages (TAMs) in lung metastases from tumor-bearing mice. Methods: BALB/c mice divided into three groups: Normal, Control and ES-treated. Tumor-bearing mice were treated with ES-transduced cells or control cells over ten days. At the end of the study, plasma was collected, and pulmonary macrophages were isolated and used for FACS or RT-PCR. ELISA tests were used to analyze plasma and cell culture supernatant cytokines. Results: ES treatment significantly reduced the levels of anti-inflammatory and pro-angiogenic cytokines, including IL4, IL-10, IL-13 and VEGF. Gene expression of M2 markers, such as IL-10, Arg-1, VEGF and YM-1, declined significantly. Flow cytometry showed a reduction in the number of M2 F4/80 + CD36 + CD206 + CD209+ macrophages and in IL-10 secretion by these cells. Reduced levels of IL-10 were also found in the culture supernatants of the ES-treated group. Conclusions: Our research corroborates previous observations that ES has an important anti-tumoral role. However, aside from promoting interferon-g secretion and an effective T cell response, we show here that this switch is extended to TAMs, complicating the maintenance of pro-tumorigenic M2 macrophages and thus favoring tumor elimination. (C) 2016 Elsevier Masson SAS. All rights reserved.en
dc.description.affiliationUniv Fed Sao Paulo, Div Nephrol, Sao Paulo, Brazil
dc.description.affiliationIPEN CNEN, Dept Biotechnol, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biol Biol Sci, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Div Nephrol, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biol Biol Sci, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFAPESP
dc.description.sponsorshipCNPq
dc.description.sponsorshipCAPES/PNPD
dc.description.sponsorshipIDFAPESP: 2011/18703-2
dc.description.sponsorshipIDCNPq: 473102/2012-9
dc.format.extent102-111
dc.identifierhttp://dx.doi.org/10.1016/j.biopha.2016.01.035
dc.identifier.citationBiomedicine & Pharmacotherapy. Paris, v. 79, p. 102-111, 2016.
dc.identifier.doi10.1016/j.biopha.2016.01.035
dc.identifier.fileWOS000373527100014.pdf
dc.identifier.issn0753-3322
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56147
dc.identifier.wosWOS:000373527100014
dc.language.isoeng
dc.publisherElsevier France-Editions Scientifiques Medicales Elsevier
dc.relation.ispartofBiomedicine & Pharmacotherapy
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectRenal cell carcinomaen
dc.subjectEndostatinen
dc.subjectTumor-associated macrophagesen
dc.titleEndostatin gene therapy inhibits intratumoral macrophage M2 polarizationen
dc.typeinfo:eu-repo/semantics/article
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