Effective Circulating Tumor Cell Isolation Using Epithelial and Mesenchymal Markers in Prostate and Pancreatic Cancer Patients

被引:7
作者
Cha, Jiwon [1 ]
Cho, Hyungseok [1 ]
Chung, Jae-Seung [2 ]
Park, Joon Seong [3 ]
Han, Ki-Ho [1 ]
机构
[1] Inje Univ, Ctr Nano Mfg, Dept Nanosci & Engn, Gimhae 50834, South Korea
[2] Inje Univ, Haeundae Paik Hosp, Dept Urol, Busan 48108, South Korea
[3] Yonsei Univ, Gangnam Severance Hosp, Dept Surg, Pancreatobiliary Canc Clin,Coll Med, Seoul 06229, South Korea
基金
新加坡国家研究基金会;
关键词
CTCs; CTC-dChip; EpCAM; microfluidics; vimentin; epithelial and mesenchymal markers; MICROFLUIDIC DEVICE; CLINICAL VALIDITY; SURFACE VIMENTIN; BREAST-CANCER; BLOOD; EMT; DISSEMINATION;
D O I
10.3390/cancers15102825
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Circulating tumor cells (CTCs) display antigenic heterogeneity between epithelial and mesenchymal phenotypes. However, most current CTC isolation methods rely on EpCAM (epithelial cell adhesion molecule) antibodies. This study introduces a more efficient CTC isolation technique utilizing both EpCAM and vimentin (mesenchymal cell marker) antibodies, alongside a lateral magnetophoretic microseparator. The effectiveness of this approach was assessed by isolating CTCs from prostate (n = 17) and pancreatic (n = 5) cancer patients using EpCAM alone, vimentin alone, and both antibodies together. Prostate cancer patients showed an average of 13.29, 11.13, and 27.95 CTCs/mL isolated using EpCAM alone, vimentin alone, and both antibodies, respectively. For pancreatic cancer patients, the averages were 1.50, 3.44, and 10.82 CTCs/mL with EpCAM alone, vimentin alone, and both antibodies, respectively. Combining antibodies more than doubled CTC isolation compared to single antibodies. Interestingly, EpCAM antibodies were more effective for localized prostate cancer, while vimentin antibodies excelled in metastatic prostate cancer isolation. Moreover, vimentin antibodies outperformed EpCAM antibodies for all pancreatic cancer patients. These results highlight that using both epithelial and mesenchymal antibodies with the lateral magnetophoretic microseparator significantly enhances CTC isolation efficiency, and that antibody choice may vary depending on cancer type and stage.
引用
收藏
页数:16
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共 48 条
[1]   Circulating Tumor Cells: Liquid Biopsy of Cancer [J].
Alix-Panabieres, Catherine ;
Pantel, Klaus .
CLINICAL CHEMISTRY, 2013, 59 (01) :110-118
[2]   Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases [J].
Allard, WJ ;
Matera, J ;
Miller, MC ;
Repollet, M ;
Connelly, MC ;
Rao, C ;
Tibbe, AGJ ;
Uhr, JW ;
Terstappen, LWMM .
CLINICAL CANCER RESEARCH, 2004, 10 (20) :6897-6904
[3]   Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data [J].
Bidard, Francois-Clement ;
Peeters, Dieter J. ;
Fehm, Tanja ;
Nole, Franco ;
Gisbert-Criado, Rafael ;
Mavroudis, Dimitrios ;
Grisanti, Salvatore ;
Generali, Daniele ;
Garcia-Saenz, Jose A. ;
Stebbing, Justin ;
Caldas, Carlos ;
Gazzaniga, Paola ;
Manso, Luis ;
Zamarchi, Rita ;
Fernandez de Lascoiti, Angela ;
De Mattos-Arruda, Leticia ;
Ignatiadis, Michail ;
Lebofsky, Ronald ;
van Laere, Steven J. ;
Meier-Stiegen, Franziska ;
Sandri, Maria-Teresa ;
Vidal-Martinez, Jose ;
Politaki, Eleni ;
Consoli, Francesca ;
Bottini, Alberto ;
Diaz-Rubio, Eduardo ;
Krell, Jonathan ;
Dawson, Sarah-Jane ;
Raimondi, Cristina ;
Rutten, Annemie ;
Janni, Wolfgang ;
Munzone, Elisabetta ;
Caranana, Vicente ;
Agelaki, Sofi A. ;
Almici, Camillo ;
Dirix, Luc ;
Solomayer, Erich-Franz ;
Zorzino, Laura ;
Johannes, Helene ;
Reis-Filho, Jorge S. ;
Pantel, Klaus ;
Pierga, Jean-Yves ;
Michiels, Stefan .
LANCET ONCOLOGY, 2014, 15 (04) :406-414
[4]   Membrane Hsp70 -A Novel Target for the Isolation of Circulating Tumor Cells After Epithelial-to-Mesenchymal Transition [J].
Breuninger, Stephanie ;
Stangl, Stefan ;
Werner, Caroline ;
Sievert, Wolfgang ;
Lobinger, Dominik ;
Foulds, Gemma A. ;
Wagner, Sarah ;
Pickhard, Anja ;
Piontek, Guido ;
Kokowski, Konrad ;
Pockley, Alan G. ;
Multhoff, Gabriele .
FRONTIERS IN ONCOLOGY, 2018, 8
[5]   Circulating tumor cells: clinical validity and utility [J].
Cabel, Luc ;
Proudhon, Charlotte ;
Gortais, Hugo ;
Loirat, Delphine ;
Coussy, Florence ;
Pierga, Jean-Yves ;
Bidard, Francois-Clement .
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 2017, 22 (03) :421-430
[6]   Dissemination and growth of cancer cells in metastatic sites [J].
Chambers, AF ;
Groom, AC ;
MacDonald, IC .
NATURE REVIEWS CANCER, 2002, 2 (08) :563-572
[7]   Subclassification of prostate cancer circulating tumor cells by nuclear size reveals very small nuclear circulating tumor cells in patients with visceral metastases [J].
Chen, Jie-Fu ;
Ho, Hao ;
Lichterman, Jake ;
Lu, Yi-Tsung ;
Zhang, Yang ;
Garcia, Mitch A. ;
Chen, Shang-Fu ;
Liang, An-Jou ;
Hodara, Elisabeth ;
Zhau, Haiyen E. ;
Hou, Shuang ;
Ahmed, Rafi S. ;
Luthringer, Daniel J. ;
Huang, Jiaoti ;
Li, Ker-Chau ;
Chung, Leland W. K. ;
Ke, Zunfu ;
Tseng, Hsian-Rong ;
Posadas, Edwin M. .
CANCER, 2015, 121 (18) :3240-3251
[8]   A disposable microfluidic device with a reusable magnetophoretic functional substrate for isolation of circulating tumor cells [J].
Cho, Hyungseok ;
Kim, Jinho ;
Jeon, Chang-Wan ;
Han, Ki-Ho .
LAB ON A CHIP, 2017, 17 (23) :4113-4123
[9]   Circulating tumor cells, disease progression, and survival in metastatic breast cancer [J].
Cristofanilli, M ;
Budd, GT ;
Ellis, MJ ;
Stopeck, A ;
Matera, J ;
Miller, MC ;
Reuben, JM ;
Doyle, GV ;
Allard, WJ ;
Terstappen, LWMM ;
Hayes, DF .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (08) :781-791
[10]   Nanomechanical analysis of cells from cancer patients [J].
Cross, Sarah E. ;
Jin, Yu-Sheng ;
Rao, Jianyu ;
Gimzewski, James K. .
NATURE NANOTECHNOLOGY, 2007, 2 (12) :780-783