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
Y1 - 2018
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.
UR - https://doi.org/10.1038/s41467-018-05793-2,
U2 - 10.1038/s41467-018-05793-2
DO - 10.1038/s41467-018-05793-2
M3 - Journal article
C2 - 30115931
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3279
ER -