Journal article
Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein
University of Copenhagen1
Department of Systems Biology, Technical University of Denmark2
British Columbia Cancer Agency3
Vancouver Prostate Centre4
Kairos Therapeutics Inc.5
Boston University School of Medicine6
Translational Genomics Research Institute7
University of British Columbia8
Retrogenix Ltd.9
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark10
Cancer Systems Biology, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark11
...and 1 morePlasmodium 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.
| Language: | English |
|---|---|
| Year: | 2015 |
| Pages: | 500-514 |
| ISSN: | 18783686 and 15356108 |
| Types: | Journal article |
| DOI: | 10.1016/j.ccell.2015.09.003 |
| ORCIDs: | 0000-0003-2207-5575 , 0000-0001-7543-9622 , 0000-0001-5865-2034 , 0000-0003-0243-2248 , 0000-0003-4282-6970 , 0000-0002-3965-5165 , 0000-0002-5594-0716 , 0000-0001-6596-3527 , 0000-0002-1279-304X , 0000-0003-2668-4992 and 0000-0002-3509-7514 |
Animals Antigens, Protozoan CD44 protein, human CSPG4 protein, human Cell Line, Tumor Chondroitin Sulfate Proteoglycans Chondroitin Sulfates Female HEK293 Cells Human Umbilical Vein Endothelial Cells Humans Hyaluronan Receptors Melanoma, Experimental Membrane Proteins Mice Molecular Targeted Therapy Oligopeptides Organ Specificity Placenta Pregnancy Recombinant Proteins Skin Neoplasms VAR2CSA protein, Plasmodium falciparum hemiasterlin
