Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein
作者： Ali Salanti , Thomas M Clausen , Mette Ø Agerbæk , Nader Al Nakouzi , Madeleine Dahlbäck
DOI: 10.1016/J.CCELL.2015.09.003
关键词: Plasmodium falciparum 、 In vivo 、 CSPG4 、 HEK 293 cells 、 Diphtheria toxin 、 Chondroitin sulfate 、 Biology 、 Glycosaminoglycan binding 、 Molecular biology 、 Glycosaminoglycan
摘要: Plasmodium falciparum engineer infected erythrocytes to present the malarial protein, VAR2CSA, which binds a distinct type chondroitin sulfate (CS) exclusively expressed in placenta. Here, we show that same CS modification is on high proportion of malignant cells and it can be specifically targeted by recombinant VAR2CSA (rVAR2). In tumors, placental-like chains are linked limited repertoire cancer-associated proteoglycans including CD44 CSPG4. The rVAR2 protein localizes tumors vivo fused diphtheria toxin or conjugated hemiasterlin compounds strongly inhibits tumor cell growth metastasis. Our data demonstrate how an evolutionarily refined parasite-derived exploited target common, but complex, malignancy-associated glycosaminoglycan modification.
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