| Literature DB >> 26461094 |
Ali Salanti1, Thomas M Clausen2, Mette Ø Agerbæk3, Nader Al Nakouzi4, Madeleine Dahlbäck5, Htoo Zarni Oo4, Sherry Lee6, Tobias Gustavsson5, Jamie R Rich7, Bradley J Hedberg7, Yang Mao8, Line Barington5, Marina A Pereira5, Janine LoBello9, Makoto Endo10, Ladan Fazli6, Jo Soden11, Chris K Wang6, Adam F Sander5, Robert Dagil5, Susan Thrane5, Peter J Holst5, Le Meng8, Francesco Favero12, Glen J Weiss13, Morten A Nielsen5, Jim Freeth11, Torsten O Nielsen14, Joseph Zaia8, Nhan L Tran9, Jeff Trent9, John S Babcook7, Thor G Theander5, Poul H Sorensen15, Mads Daugaard16.
Abstract
Plasmodium falciparum 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.Entities:
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Year: 2015 PMID： 26461094 PMCID： PMC4790448 DOI： 10.1016/j.ccell.2015.09.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743