Abstract 2325: Destruction of circulating tumor cells by fluid shear stresses generated in a microfluidic system

Tumor cells are hypothesized to use proteolytic enzymes to facilitate invasion. Whether circulating tumor cells (CTCs) secrete these enzymes to aid metastasis is unknown. A quantitative and high-throughput approach to assay CTC secretion is needed to address this question. We developed an integrated microfluidic system that concentrates rare cancer cells >100,000-fold from 1 mL of whole blood into ∼50,000 2-nL drops composed of assay reagents within 15 min. The system isolates CTCs by size, exchanges fluid around CTCs to remove contaminants, introduces a matrix metalloprotease (MMP) substrate, and encapsulates CTCs into microdroplets. We found CTCs from prostate cancer patients possessed above baseline levels of MMP activity (1.7- to 200-fold). Activity of CTCs was generally higher than leukocytes from the same patient (average CTC/leukocyte MMP activity ratio, 2.6 ± 1.5). Higher MMP activity of CTCs suggests active proteolytic processes that may facilitate invasion or immune evasion and be relevant phenotypic biomarkers enabling companion diagnostics for anti-MMP therapies.

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Functional magnetic nanoparticles for circulating tumor cells screening in integrated microfluidic system

2014 International Conference on Manipulation, Manufacturing and Measurement on the Nanoscale (3M-NANO) ◽

10.1109/3m-nano.2014.7057335 ◽

2014 ◽

Author(s):

Jiao Wu ◽

Yaling Li ◽

Kun Qian ◽

Xiaojing Zhang ◽

Ting Shen

Keyword(s):

Magnetic Nanoparticles ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Microfluidic System

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Selective isolation of magnetic nanoparticle-mediated heterogeneity subpopulation of circulating tumor cells using magnetic gradient based microfluidic system

Biosensors and Bioelectronics ◽

10.1016/j.bios.2016.08.002 ◽

2017 ◽

Vol 88 ◽

pp. 153-158 ◽

Cited By ~ 34

Author(s):

Bongseop Kwak ◽

Jaehun Lee ◽

Dongkyu Lee ◽

Kangho Lee ◽

Ohwon Kwon ◽

...

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Magnetic Nanoparticle ◽

Microfluidic System ◽

Selective Isolation ◽

Magnetic Gradient ◽

Gradient Based

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Integrative Analysis and Machine Learning based Characterization of Single Circulating Tumor Cells

Journal of Clinical Medicine ◽

10.3390/jcm9041206 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1206 ◽

Cited By ~ 5

Author(s):

Arvind Iyer ◽

Krishan Gupta ◽

Shreya Sharma ◽

Kishore Hari ◽

Yi Fang Lee ◽

...

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Expression Profiles ◽

Gene Expression Pattern ◽

Microfluidic System ◽

Integrative Analysis ◽

Label Free ◽

Peripheral Blood Mononuclear ◽

Cell Expression

We collated publicly available single-cell expression profiles of circulating tumor cells (CTCs) and showed that CTCs across cancers lie on a near-perfect continuum of epithelial to mesenchymal (EMT) transition. Integrative analysis of CTC transcriptomes also highlighted the inverse gene expression pattern between PD-L1 and MHC, which is implicated in cancer immunotherapy. We used the CTCs expression profiles in tandem with publicly available peripheral blood mononuclear cell (PBMC) transcriptomes to train a classifier that accurately recognizes CTCs of diverse phenotype. Further, we used this classifier to validate circulating breast tumor cells captured using a newly developed microfluidic system for label-free enrichment of CTCs.

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