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丝氨酸蛋白酶抑制剂衍生肽具有抗血管生成作用,并能抑制乳腺癌异种移植瘤的生长。

Serpin-derived peptides are antiangiogenic and suppress breast tumor xenograft growth.

机构信息

Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

出版信息

Transl Oncol. 2012 Apr;5(2):92-7. doi: 10.1593/tlo.11244. Epub 2012 Apr 1.

Abstract

Angiogenesis is the formation of neovasculature from preexisting microvessels. Several endogenous proteins regulate the balance of vessel formation and regression in the body including pigment epithelium-derived factor (PEDF), which has been shown to be antiangiogenic and to suppress tumor growth. Using sequence homology and bioinformatics, we previously identified several peptide sequences homologous to an active region of PEDF existing in multiple proteins in the human proteome. These short 11-mer peptides are found in a DEAH box helicase protein, CKIP-1 and caspase 10, and show similar activity in altering endothelial cell adhesion, migration and inducing apoptosis.We tested the peptide derived from DEAH box helicase protein in a triple-negative MDA-MB-231 breast orthotopic xenograft model in severe combined immunodeficient mice and show significant tumor suppression.

摘要

血管生成是指从预先存在的微血管形成新的血管。几种内源性蛋白调节体内血管形成和退化的平衡,包括色素上皮衍生因子(PEDF),它具有抗血管生成和抑制肿瘤生长的作用。我们之前使用序列同源性和生物信息学,在人类蛋白质组中发现了几种与 PEDF 的一个活性区域同源的短肽序列。这些 11 个氨基酸的肽存在于 DEAH 盒解旋酶蛋白、CKIP-1 和半胱天冬酶 10 中,并表现出相似的改变内皮细胞黏附、迁移和诱导细胞凋亡的活性。我们在严重联合免疫缺陷小鼠的三阴性 MDA-MB-231 乳腺原位异种移植模型中测试了来源于 DEAH 盒解旋酶蛋白的肽,结果显示肿瘤显著抑制。

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