Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein

Ali Salanti; Thomas M. Clausen; Mette O. 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 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 O. 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 Tran, Jeff Trent, John S. Babcook, Thor G. Theander, Poul H. Sorensen, Mads Daugaard

Research output: Contribution to journal › Article

72 Scopus citations

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.

Original language	English (US)
Article number	2143
Pages (from-to)	500-514
Number of pages	15
Journal	Cancer Cell
Volume	28
Issue number	4
DOIs	https://doi.org/10.1016/j.ccell.2015.09.003
State	Published - Oct 12 2015
Externally published	Yes

ASJC Scopus subject areas

Medicine(all)
Oncology
Cell Biology
Cancer Research

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Salanti, A., Clausen, T. M., Agerbæk, M. O., 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), 500-514. [2143]. https://doi.org/10.1016/j.ccell.2015.09.003

Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein. / Salanti, Ali; Clausen, Thomas M.; Agerbæk, Mette O.; Al Nakouzi, Nader; Dahlbäck, Madeleine; Oo, Htoo Z.; Lee, Sherry; Gustavsson, Tobias; Rich, Jamie R.; Hedberg, Bradley J.; Mao, Yang; Barington, Line; Pereira, Marina A.; LoBello, Janine; Endo, Makoto; Fazli, Ladan; Soden, Jo; Wang, Chris K.; Sander, Adam F.; Dagil, Robert; Thrane, Susan; Holst, Peter J.; Meng, Le; Favero, Francesco; Weiss, Glen J.; Nielsen, Morten A.; Freeth, Jim; Nielsen, Torsten O.; Zaia, Joseph; Tran, Nhan; Trent, Jeff; Babcook, John S.; Theander, Thor G.; Sorensen, Poul H.; Daugaard, Mads.

In: Cancer Cell, Vol. 28, No. 4, 2143, 12.10.2015, p. 500-514.

Research output: Contribution to journal › Article

Salanti, A, Clausen, TM, Agerbæk, MO, 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, N, Trent, J, Babcook, JS, Theander, TG, Sorensen, PH & Daugaard, M 2015, 'Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein', Cancer Cell, vol. 28, no. 4, 2143, pp. 500-514. https://doi.org/10.1016/j.ccell.2015.09.003

Salanti, Ali ; Clausen, Thomas M. ; Agerbæk, Mette O. ; Al Nakouzi, Nader ; Dahlbäck, Madeleine ; Oo, Htoo Z. ; Lee, Sherry ; Gustavsson, Tobias ; Rich, Jamie R. ; Hedberg, Bradley J. ; Mao, Yang ; Barington, Line ; Pereira, Marina A. ; LoBello, Janine ; Endo, Makoto ; Fazli, Ladan ; Soden, Jo ; Wang, Chris K. ; Sander, Adam F. ; Dagil, Robert ; Thrane, Susan ; Holst, Peter J. ; Meng, Le ; Favero, Francesco ; Weiss, Glen J. ; Nielsen, Morten A. ; Freeth, Jim ; Nielsen, Torsten O. ; Zaia, Joseph ; Tran, Nhan ; Trent, Jeff ; Babcook, John S. ; Theander, Thor G. ; Sorensen, Poul H. ; Daugaard, Mads. / Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein. In: Cancer Cell. 2015 ; Vol. 28, No. 4. pp. 500-514.

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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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