Functional profiling of circulating tumor cells with an integrated vortex capture and single-cell protease activity assay.
Proc Natl Acad Sci U S A
; 115(40): 9986-9991, 2018 10 02.
Article
em En
| MEDLINE
| ID: mdl-30224472
ABSTRACT
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 â¼50,000 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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Base de dados:
MEDLINE
Assunto principal:
Separação Celular
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Colagenases
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Técnicas Analíticas Microfluídicas
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Dispositivos Lab-On-A-Chip
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Células Neoplásicas Circulantes
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Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article