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Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein

2015; Cell Press; Volume: 28; Issue: 4 Linguagem: Inglês

10.1016/j.ccell.2015.09.003

1878-3686

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

HIV Research and Treatment

Summary 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.