Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein

Ali Salanti; Thomas M Clausen; Mette Ø Agerbæk; Nader Al Nakouzi; Madeleine Dahlbäck; Htoo Z Oo; Sherry Lee; Tobias Gustavsson; Jamie R Rich; Bradley J Hedberg; Yang Mao; Line Barington; Marina A Pereira; Janine LoBello; Makoto Endo; Ladan Fazli; Jo Soden; Chris K Wang; Adam F Sander; Robert Dagil; Susan Thrane; Peter J 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

doi:10.1016/j.ccell.2015.09.003

Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein

Ali Salanti, Thomas M Clausen, Mette Ø Agerbæk, Nader Al Nakouzi, Madeleine Dahlbäck, Htoo Z Oo, Sherry Lee, Tobias Gustavsson, Jamie R Rich, Bradley J Hedberg, Yang Mao, Line Barington, Marina A Pereira, Janine LoBello, Makoto Endo, Ladan Fazli, Jo Soden, Chris K Wang, Adam F Sander, Robert DagilSusan Thrane, Peter J 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

93 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Cancer Cell
Vol/bind	28
Udgave nummer	4
Sider (fra-til)	500-14
Antal sider	15
ISSN	1535-6108
DOI	https://doi.org/10.1016/j.ccell.2015.09.003
Status	Udgivet - 12 okt. 2015

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10.1016/j.ccell.2015.09.003

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Salanti, A., Clausen, T. M., Agerbæk, M. Ø., Al Nakouzi, N., Dahlbäck, M., Oo, H. Z., Lee, S., Gustavsson, T., Rich, J. R., Hedberg, B. J., Mao, Y., Barington, L., Pereira, M. A., LoBello, J., Endo, M., Fazli, L., Soden, J., Wang, C. K., Sander, A. F., ... Daugaard, M. (2015). Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein. Cancer Cell, 28(4), 500-14. https://doi.org/10.1016/j.ccell.2015.09.003

Salanti, A , Clausen, TM , Agerbæk, MØ, Al Nakouzi, N, Dahlbäck, M, Oo, HZ, Lee, S, Gustavsson, T, Rich, JR, Hedberg, BJ, Mao, Y, Barington, L , Pereira, MA, LoBello, J, Endo, M, Fazli, L, Soden, J, Wang, CK, Sander, AF, Dagil, R , Thrane, S , Holst, PJ, Meng, L, Favero, F, Weiss, GJ, Nielsen, MA, Freeth, J, Nielsen, TO, Zaia, J, Tran, NL, Trent, J, Babcook, JS, Theander, TG, Sorensen, PH & Daugaard, M 2015, 'Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein', Cancer Cell, bind 28, nr. 4, s. 500-14. https://doi.org/10.1016/j.ccell.2015.09.003

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title = "Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein",

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.",

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AU - Salanti, Ali

AU - Clausen, Thomas M

AU - Agerbæk, Mette Ø

AU - Al Nakouzi, Nader

AU - Dahlbäck, Madeleine

AU - Oo, Htoo Z

AU - Lee, Sherry

AU - Gustavsson, Tobias

AU - Rich, Jamie R

AU - Hedberg, Bradley J

AU - Mao, Yang

AU - Barington, Line

AU - Pereira, Marina A

AU - LoBello, Janine

AU - Endo, Makoto

AU - Fazli, Ladan

AU - Soden, Jo

AU - Wang, Chris K

AU - Sander, Adam F

AU - Dagil, Robert

AU - Thrane, Susan

AU - Holst, Peter J

AU - Meng, Le

AU - Favero, Francesco

AU - Weiss, Glen J

AU - Nielsen, Morten A

AU - Freeth, Jim

AU - Nielsen, Torsten O

AU - Zaia, Joseph

AU - Tran, Nhan L

AU - Trent, Jeff

AU - Babcook, John S

AU - Theander, Thor G

AU - Sorensen, Poul H

AU - Daugaard, Mads

PY - 2015/10/12

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N2 - 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.

AB - 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.

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SP - 500

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JO - Cancer Cell

JF - Cancer Cell

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Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein

Abstract

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