Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein

Salanti Ali; Clausen Thomas M.; Agerbaek Mette O.; Al Nakouzi Nader; Dahlback Madeleine; Oo Htoo Z.; Lee Sherry; Gustavsson Tobias; Rich Jamie R.; Hedberg Bradley J.; Mao Yang; Barington Line; Pereira Marina A.; LoBello Janine; Endo Makoto; Fazli Ladan; Soden Jo; Wang Chris K.; Sander Adam F.; Dagil Robert; Thrane Susan; Holst Peter J.; Le Meng; Favero Francesco; Weiss Glen J.; Nielsen Morten A.; Freeth Jim; Nielsen Torsten O.; Zaia Joseph; Tran Nhan L.; Trent Jeff; Babcook John S.; Theander Thor G.; Sorensen Poul H.; Daugaard Mads

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Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein

机译：通过糖胺聚糖结合疟疾蛋白靶向人类癌症。

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Plasmodiumfalciparum engineer infected erythrocytes to present the malarial protein, VAR2CSA, which binds a distinct type chondroitin sulfate (CS) exclusively expressed in the placenta. Here, we show that the same CS modification is present on a high proportion of malignant cells and that it can be specifically targeted by recombinant VAR2CSA (rVAR2). In tumors, placental-like CS chains are linked to a limited repertoire of cancer-associated proteoglycans including CD44 and CSPG4. The rVAR2 protein localizes to tumors in vivo and rVAR2 fused to diphtheria toxin or conjugated to hemiasterlin compounds strongly inhibits in vivo tumor cell growth and metastasis. Our data demonstrate how an evolutionarily refined parasite-derived protein can be exploited to target a common, but complex, malignancy-associated glycosaminoglycan modification.

机译：恶性疟原虫工程师感染了红细胞，呈递出疟疾蛋白VAR2CSA，该蛋白与胎盘中专门表达的独特类型的硫酸软骨素（CS）结合。在这里，我们表明相同的CS修饰存在于高比例的恶性细胞上，并且可以被重组VAR2CSA（rVAR2）特异性靶向。在肿瘤中，胎盘样CS链与癌症相关的蛋白聚糖（包括CD44和CSPG4）的有限组成部分相关。 rVAR2蛋白在体内定位于肿瘤，与白喉毒素融合或与半胱氨酸化合物缀合的rVAR2强烈抑制体内肿瘤细胞的生长和转移。我们的数据表明，如何利用进化上精制的寄生虫衍生蛋白来靶向常见但复杂的恶性肿瘤相关的糖胺聚糖修饰。

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《Cancer Cell》 |2015年第4期|共15页
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Salanti Ali; Clausen Thomas M.; Agerbaek Mette O.; Al Nakouzi Nader; Dahlback Madeleine; Oo Htoo Z.; Lee Sherry; Gustavsson Tobias; Rich Jamie R.; Hedberg Bradley J.; Mao Yang; Barington Line; Pereira Marina A.; LoBello Janine; Endo Makoto; Fazli Ladan; Soden Jo; Wang Chris K.; Sander Adam F.; Dagil Robert; Thrane Susan; Holst Peter J.; Le Meng; Favero Francesco; Weiss Glen J.; Nielsen Morten A.; Freeth Jim; Nielsen Torsten O.; Zaia Joseph; Tran Nhan L.; Trent Jeff; Babcook John S.; Theander Thor G.; Sorensen Poul H.; Daugaard Mads;
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正文语种 eng
中图分类肿瘤学;
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1. Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein [J] . Salanti Ali, Clausen Thomas M., Agerbaek Mette O., Cancer Cell . 2015,第4期

机译：通过糖胺聚糖结合疟疾蛋白靶向人类癌症。
2. Fighting Cancer Using an Oncofetal Glycosaminoglycan-Binding Protein from Malaria Parasites [J] . Agerbaek Mette O., Bang-Christensen Sara, Salanti Ali Trends In Parasitology . 2019,第3期

机译：使用来自疟疾寄生虫的肿瘤糖胺聚糖结合蛋白对抗癌症
3. Inhibition of the Inositol Requiring Protein 1α- X-Box Binding Protein-1 Pathway as a Promising Therapeutic Target for Human Prostate Cancer [J] . Ahmad M. Khalil, Ahmad Y. Alghadi, Rahaf M. T. Shahen, Journal of Cancer Research and Treatment . 2018,第3期

机译：抑制肌醇需要蛋白1α-X-Box结合蛋白-1途径作为人类前列腺癌的有希望的治疗靶点。
4. Characterization of heparin interactions with its client proteins: mapping minimal protein-binding domains within glycosaminoglycan chains using top-down mass spectrometry [C] . Yunlong Zhao, Igor A. Kaltashov ASMS Conference on Mass Spectrometry and Allied Topics . 2016

机译：肝素与其客户蛋白相互作用的表征：使用自上向下质谱法将糖胺聚糖链中的最小蛋白质结合结构域映射缩放最小蛋白质结合结构域
5. Identification and characterization of binding target proteins of cancer stem cell inhibitor salinomycin in human neuroblastoma [D] . Zhou, Shuang. 2015

机译：人神经母细胞瘤中癌症干细胞抑制剂沙利霉素的结合靶蛋白的鉴定与表征
6. Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein [O] . Ali Salanti, Thomas M. Clausen, Mette Ø. Agerbæk, -1

机译：通过糖胺聚糖结合疟疾蛋白靶向人类癌症。
7. Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein [O] . Salanti Ali, Clausen Thomas M., Agerbæk Mette Ø., 2015

机译：通过糖胺聚糖结合疟疾蛋白靶向人类癌症。
8. Targeting Common but Complex Proteoglycans on Breast Cancer Cells and Stem Cells Using Evolutionary Refined Malaria Proteins. [R] . Daugaard, M. 2017

机译：使用进化精制疟疾蛋白靶向乳腺癌细胞和干细胞上常见但复杂的蛋白多糖。

Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein

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