The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner

Mette Ø Agerbæk; Sara R Bang-Christensen; Ming-Hsin Yang; Thomas M Clausen; Marina A Pereira; Shreya Sharma; Sisse B Ditlev; Morten A Nielsen; Swati Choudhary; Tobias Gustavsson; Poul H Sorensen; Tim Meyer; David Propper; Jonathan Shamash; Thor G Theander; Alexandra Aicher; Mads Daugaard; Christopher Heeschen; Ali Salanti

doi:10.1038/s41467-018-05793-2

The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner

Mette Ø Agerbæk, Sara R Bang-Christensen, Ming-Hsin Yang, Thomas M Clausen, Marina A Pereira, Shreya Sharma, Sisse B Ditlev, Morten A Nielsen, Swati Choudhary, Tobias Gustavsson, Poul H Sorensen, Tim Meyer, David Propper, Jonathan Shamash, Thor G Theander, Alexandra Aicher, Mads Daugaard, Christopher Heeschen, Ali Salanti

139 Citations (Scopus)

Abstract

Isolation of metastatic circulating tumor cells (CTCs) from cancer patients is of high value for disease monitoring and molecular characterization. Despite the development of many new CTC isolation platforms in the last decade, their isolation and detection has remained a challenge due to the lack of specific and sensitive markers. In this feasibility study, we present a method for CTC isolation based on the specific binding of the malaria rVAR2 protein to oncofetal chondroitin sulfate (ofCS). We show that rVAR2 efficiently captures CTCs from hepatic, lung, pancreatic, and prostate carcinoma patients with minimal contamination of peripheral blood mononuclear cells. Expression of ofCS is present on epithelial and mesenchymal cancer cells and is equally preserved during epithelial-mesenchymal transition of cancer cells. In 25 stage I-IV prostate cancer patient samples, CTC enumeration significantly correlates with disease stage. Lastly, rVAR2 targets a larger and more diverse population of CTCs compared to anti-EpCAM strategies.

Original language	English
Journal	Nature Communications
Volume	9
Issue number	1
Pages (from-to)	3279
ISSN	2041-1722
DOIs	https://doi.org/10.1038/s41467-018-05793-2
Publication status	Published - 16 Aug 2018

Keywords

Adaptation, Physiological
Antigens, Protozoan/metabolism
Cell Line, Tumor
Cell Separation
Epithelial Cell Adhesion Molecule/metabolism
Epithelial Cells/metabolism
Epithelial-Mesenchymal Transition
Humans
Leukocytes, Mononuclear/metabolism
Magnetics
Male
Mesoderm/metabolism
Microspheres
Neoplasm Staging
Neoplastic Cells, Circulating/metabolism
Pancreatic Neoplasms/blood
Prostatic Neoplasms/metabolism
Protein Binding
Proto-Oncogene Proteins p21(ras)/genetics
Recombinant Proteins/metabolism

Access to Document

10.1038/s41467-018-05793-2

Cite this

Agerbæk, M. Ø., Bang-Christensen, S. R., Yang, M.-H., Clausen, T. M., Pereira, M. A., Sharma, S., Ditlev, S. B., Nielsen, M. A., Choudhary, S., Gustavsson, T., Sorensen, P. H., Meyer, T., Propper, D., Shamash, J., Theander, T. G., Aicher, A., Daugaard, M., Heeschen, C., & Salanti, A. (2018). The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner. Nature Communications, 9(1), 3279. https://doi.org/10.1038/s41467-018-05793-2

Agerbæk, MØ, Bang-Christensen, SR, Yang, M-H, Clausen, TM, Pereira, MA, Sharma, S, Ditlev, SB, Nielsen, MA, Choudhary, S, Gustavsson, T, Sorensen, PH, Meyer, T, Propper, D, Shamash, J, Theander, TG, Aicher, A, Daugaard, M, Heeschen, C & Salanti, A 2018, 'The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner', Nature Communications, vol. 9, no. 1, pp. 3279. https://doi.org/10.1038/s41467-018-05793-2

@article{ea6cd225833e4cc4bad546c845358fbe,

title = "The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner",

abstract = "Isolation of metastatic circulating tumor cells (CTCs) from cancer patients is of high value for disease monitoring and molecular characterization. Despite the development of many new CTC isolation platforms in the last decade, their isolation and detection has remained a challenge due to the lack of specific and sensitive markers. In this feasibility study, we present a method for CTC isolation based on the specific binding of the malaria rVAR2 protein to oncofetal chondroitin sulfate (ofCS). We show that rVAR2 efficiently captures CTCs from hepatic, lung, pancreatic, and prostate carcinoma patients with minimal contamination of peripheral blood mononuclear cells. Expression of ofCS is present on epithelial and mesenchymal cancer cells and is equally preserved during epithelial-mesenchymal transition of cancer cells. In 25 stage I-IV prostate cancer patient samples, CTC enumeration significantly correlates with disease stage. Lastly, rVAR2 targets a larger and more diverse population of CTCs compared to anti-EpCAM strategies.",

keywords = "Adaptation, Physiological, Antigens, Protozoan/metabolism, Cell Line, Tumor, Cell Separation, Epithelial Cell Adhesion Molecule/metabolism, Epithelial Cells/metabolism, Epithelial-Mesenchymal Transition, Humans, Leukocytes, Mononuclear/metabolism, Magnetics, Male, Mesoderm/metabolism, Microspheres, Neoplasm Staging, Neoplastic Cells, Circulating/metabolism, Pancreatic Neoplasms/blood, Prostatic Neoplasms/metabolism, Protein Binding, Proto-Oncogene Proteins p21(ras)/genetics, Recombinant Proteins/metabolism",

author = "Agerb{\ae}k, \{Mette {\O}\} and Bang-Christensen, \{Sara R\} and Ming-Hsin Yang and Clausen, \{Thomas M\} and Pereira, \{Marina A\} and Shreya Sharma and Ditlev, \{Sisse B\} and Nielsen, \{Morten A\} and Swati Choudhary and Tobias Gustavsson and Sorensen, \{Poul H\} and Tim Meyer and David Propper and Jonathan Shamash and Theander, \{Thor G\} and Alexandra Aicher and Mads Daugaard and Christopher Heeschen and Ali Salanti",

year = "2018",

month = aug,

day = "16",

doi = "10.1038/s41467-018-05793-2",

language = "English",

volume = "9",

pages = "3279",

journal = "Nature Communications",

issn = "2041-1722",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner

AU - Agerbæk, Mette Ø

AU - Bang-Christensen, Sara R

AU - Yang, Ming-Hsin

AU - Clausen, Thomas M

AU - Pereira, Marina A

AU - Sharma, Shreya

AU - Ditlev, Sisse B

AU - Nielsen, Morten A

AU - Choudhary, Swati

AU - Gustavsson, Tobias

AU - Sorensen, Poul H

AU - Meyer, Tim

AU - Propper, David

AU - Shamash, Jonathan

AU - Theander, Thor G

AU - Aicher, Alexandra

AU - Daugaard, Mads

AU - Heeschen, Christopher

AU - Salanti, Ali

PY - 2018/8/16

Y1 - 2018/8/16

N2 - Isolation of metastatic circulating tumor cells (CTCs) from cancer patients is of high value for disease monitoring and molecular characterization. Despite the development of many new CTC isolation platforms in the last decade, their isolation and detection has remained a challenge due to the lack of specific and sensitive markers. In this feasibility study, we present a method for CTC isolation based on the specific binding of the malaria rVAR2 protein to oncofetal chondroitin sulfate (ofCS). We show that rVAR2 efficiently captures CTCs from hepatic, lung, pancreatic, and prostate carcinoma patients with minimal contamination of peripheral blood mononuclear cells. Expression of ofCS is present on epithelial and mesenchymal cancer cells and is equally preserved during epithelial-mesenchymal transition of cancer cells. In 25 stage I-IV prostate cancer patient samples, CTC enumeration significantly correlates with disease stage. Lastly, rVAR2 targets a larger and more diverse population of CTCs compared to anti-EpCAM strategies.

AB - Isolation of metastatic circulating tumor cells (CTCs) from cancer patients is of high value for disease monitoring and molecular characterization. Despite the development of many new CTC isolation platforms in the last decade, their isolation and detection has remained a challenge due to the lack of specific and sensitive markers. In this feasibility study, we present a method for CTC isolation based on the specific binding of the malaria rVAR2 protein to oncofetal chondroitin sulfate (ofCS). We show that rVAR2 efficiently captures CTCs from hepatic, lung, pancreatic, and prostate carcinoma patients with minimal contamination of peripheral blood mononuclear cells. Expression of ofCS is present on epithelial and mesenchymal cancer cells and is equally preserved during epithelial-mesenchymal transition of cancer cells. In 25 stage I-IV prostate cancer patient samples, CTC enumeration significantly correlates with disease stage. Lastly, rVAR2 targets a larger and more diverse population of CTCs compared to anti-EpCAM strategies.

KW - Adaptation, Physiological

KW - Antigens, Protozoan/metabolism

KW - Cell Line, Tumor

KW - Cell Separation

KW - Epithelial Cell Adhesion Molecule/metabolism

KW - Epithelial Cells/metabolism

KW - Epithelial-Mesenchymal Transition

KW - Humans

KW - Leukocytes, Mononuclear/metabolism

KW - Magnetics

KW - Male

KW - Mesoderm/metabolism

KW - Microspheres

KW - Neoplasm Staging

KW - Neoplastic Cells, Circulating/metabolism

KW - Pancreatic Neoplasms/blood

KW - Prostatic Neoplasms/metabolism

KW - Protein Binding

KW - Proto-Oncogene Proteins p21(ras)/genetics

KW - Recombinant Proteins/metabolism

UR - https://www.scopus.com/pages/publications/85051524776

U2 - 10.1038/s41467-018-05793-2

DO - 10.1038/s41467-018-05793-2

M3 - Journal article

C2 - 30115931

SN - 2041-1722

VL - 9

SP - 3279

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this