Endostatin gene therapy inhibits intratumoral macrophage M2 polarization
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Biomedicine and Pharmacotherapy
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Background: 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 Tcell response, we show here that
this switch is extended to TAMs, complicating the maintenance of pro-tumorigenic M2 macrophages and
thus favoring tumor elimination.
Como referenciar
FOGUER, KAREN; BRAGA, MARINA de S.; PERON, JEAN P.S.; BORTOLUCI, KARINA R.; BELLINI, MARIA H. Endostatin gene therapy inhibits intratumoral macrophage M2 polarization. Biomedicine and Pharmacotherapy, v. 79, p. 102-111, 2016. DOI: 10.1016/j.biopha.2016.01.035. Disponível em: http://repositorio.ipen.br/handle/123456789/25799. Acesso em: 30 Dec 2025.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.