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硫酸乙酰肝素结合肽在三阴性乳腺癌肿瘤进展中的作用

The Heparan Sulfate Binding Peptide in Tumor Progression of Triple-Negative Breast Cancer.

作者信息

Melo Carina Mucciolo, Wang Huawei, Fujimura Ken, Strnadel Jan, Meneghetti Maria Cecília Zorél, Nader Helena Bonciani, Klemke Richard L, Pinhal Maria Aparecida Silva

机构信息

Department of Biochemistry/Molecular Biology, Universidade Federal de São Paulo, São Paulo, Brazil.

Department of Biochemistry, Faculdade de Medicina do ABC, Santo André, Brazil.

出版信息

Front Oncol. 2021 Aug 4;11:697626. doi: 10.3389/fonc.2021.697626. eCollection 2021.

Abstract

Angiogenesis is the formation of new vessels from pre-existing vasculature. The heparan sulfate chains from endothelial cell proteoglycans interact with the major angiogenic factors, regulating blood vessels´ formation. Since the FDA´s first approval, anti-angiogenic therapy has shown tumor progression inhibition and increased patient survival. Previous work in our group has selected an HS-binding peptide using a phage display system. Therefore, we investigated the effect of the selected peptide in angiogenesis and tumor progression. The HS-binding peptide showed a higher affinity for heparin N-sulfated. The HS-binding peptide was able to inhibit the proliferation of human endothelial umbilical cord cells (HUVEC) by modulation of FGF-2. It was verified a significant decrease in the tube formation of human endothelial cells and capillary formation of mice aorta treated with HS-binding peptide. HS-binding peptide also inhibited the formation of sub-intestinal blood vessels in zebrafish embryos. Additionally, in zebrafish embryos, the tumor size decreased after treatment with HS-binding peptide.

摘要

血管生成是指从预先存在的脉管系统形成新的血管。内皮细胞蛋白聚糖的硫酸乙酰肝素链与主要血管生成因子相互作用,调节血管的形成。自美国食品药品监督管理局首次批准以来,抗血管生成疗法已显示出抑制肿瘤进展并提高患者生存率。我们小组之前的工作使用噬菌体展示系统筛选出了一种硫酸乙酰肝素结合肽。因此,我们研究了所选肽对血管生成和肿瘤进展的影响。该硫酸乙酰肝素结合肽对硫酸化N-肝素具有更高的亲和力。该硫酸乙酰肝素结合肽能够通过调节FGF-2来抑制人脐静脉内皮细胞(HUVEC)的增殖。经证实,用硫酸乙酰肝素结合肽处理的人内皮细胞的管形成和小鼠主动脉的毛细血管形成均显著减少。硫酸乙酰肝素结合肽还抑制斑马鱼胚胎中肠下血管的形成。此外,在斑马鱼胚胎中,用硫酸乙酰肝素结合肽处理后肿瘤大小减小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eeca/8372403/c82ea1fb0f0a/fonc-11-697626-g001.jpg

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