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

被引：120

作者：

Agerbaek, Mette O. ^{[1
,2
,3
,4
]}

Bang-Christensen, Sara R. ^{[1
,2
]}

Yang, Ming-Hsin ^{[5
,6
]}

Clausen, Thomas M. ^{[1
,2
,3
,4
]}

Pereira, Marina A. ^{[1
,2
]}

Sharma, Shreya ^{[5
]}

Ditlev, Sisse B. ^{[1
,2
]}

Nielsen, Morten A. ^{[1
,2
]}

Choudhary, Swati ^{[1
,2
]}

Gustavsson, Tobias ^{[1
,2
]}

Sorensen, Poul H. ^{[7
]}

Meyer, Tim ^{[8
]}

Propper, David ^{[9
]}

Shamash, Jonathan ^{[9
]}

Theander, Thor G. ^{[1
,2
]}

Aicher, Alexandra ^{[5
]}

Daugaard, Mads ^{[3
,4
]}

Heeschen, Christopher ^{[5
,10
]}

Salanti, Ali ^{[1
,2
]}

机构：

[1] Univ Copenhagen, Dept Immunol & Microbiol, Ctr Med Parasitol, DK-2200 Copenhagen, Denmark

[2] Copenhagen Univ Hosp, Dept Infect Dis, DK-2200 Copenhagen, Denmark

[3] Vancouver Prostate Ctr, Vancouver V6H 3Z6, BC, Canada

[4] Univ British Columbia, Dept Urol Sci, Vancouver, BC V5Z 1M9, Canada

[5] Queen Mary Univ London, Barts Canc Inst, Stem Cells Canc & Ageing, London EC1M 6BQ, England

[6] Triserv Gen Hosp, Natl Def Med Ctr, Dept Surg, Div Urol, Taipei 11490, Taiwan

[7] British Columbia Canc Res Ctr, Dept Mol Oncol, Vancouver, BC V5Z 1L3, Canada

[8] UCL, UCL Canc Inst, London WC1E 6BT, England

[9] Barts Hlth NHS, Dept Med Oncol, London EC1A 7BE, England

[10] Univ New South Wales, Sch Med Sci, Sydney, NSW 2052, Australia

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

欧洲研究理事会;

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; CANCER STEM-CELLS; HUMAN PANCREATIC-CANCER; LUNG-CANCER; BREAST-CANCER; PROGNOSTIC-SIGNIFICANCE; CARCINOMA METASTASIS; CHONDROITIN SULFATE; PLACENTAL MALARIA; PROSTATE-CANCER;

D O I：

10.1038/s41467-018-05793-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

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