Journal
CANCER CELL
Volume 28, Issue 4, Pages 500-514Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2015.09.003
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Funding
- Novo Nordisk Foundation
- Danish Cancer Society
- Stand Up To Cancer - St. Baldrick's Pediatric Dream Team Translational Research Grant [SU2C-AACR-DT1113]
- The Danish Cancer Society [R71-A4970] Funding Source: researchfish
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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.
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