Isolation of rare circulating tumour cells in cancer patients by microchip technology

Out of circulation Viable tumour-derived epithelial cells — or circulating tumour cells (CTCs) — are found in peripheral blood from cancer patients, and are the probable origin of intractable metastatic disease. The isolation of such cells from cancer patients has been proven to be very difficult, p...

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Vydané v:	Nature Ročník 450; číslo 7173; s. 1235 - 1239
Hlavní autori:	Nagrath, Sunitha, Sequist, Lecia V., Maheswaran, Shyamala, Bell, Daphne W., Irimia, Daniel, Ulkus, Lindsey, Smith, Matthew R., Kwak, Eunice L., Digumarthy, Subba, Muzikansky, Alona, Ryan, Paula, Balis, Ulysses J., Tompkins, Ronald G., Haber, Daniel A., Toner, Mehmet
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 20.12.2007 Nature Publishing Nature Publishing Group
Predmet:	Biological and medical sciences Blood Cancer Cell Separation - methods Cells Female Humanities and Social Sciences Humans letter Male Medical diagnosis Medical research Medical sciences Microarray Analysis - instrumentation Microarray Analysis - methods Microfluidics - instrumentation Microfluidics - methods Monitoring multidisciplinary Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Neoplasm Metastasis Neoplasms - blood Neoplasms - diagnosis Neoplasms - drug therapy Neoplasms - pathology Neoplastic Cells, Circulating - pathology Oncology Prostate cancer Science Science (multidisciplinary) Semiconductors Sensitivity and Specificity Stem cells Subpopulations Tumors Human Scanning electron microscopy Cell sorter Anatomic pathology Cancerology Diagnosis Malignant tumor Tumor cell Cancer
ISSN:	0028-0836, 1476-4687, 1476-4687, 1476-4679
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Shrnutí:	Out of circulation Viable tumour-derived epithelial cells — or circulating tumour cells (CTCs) — are found in peripheral blood from cancer patients, and are the probable origin of intractable metastatic disease. The isolation of such cells from cancer patients has been proven to be very difficult, primarily due to their exceedingly low numbers in peripheral blood. Now a microfluidic platform 'CTC-chip' has been developed, capable of selective, efficient separation of CTCs from the blood of cancer patients. This new tool could be used in the detection and diagnosis of cancers, and to monitor an individual patient's response to therapy. A microfluidic platform that is capable of efficiently and selectively separating viable circulating tumour cells (CTCs) from peripheral blood samples has been developed. Low levels of CTCs in the peripheral blood of patients with various cancers were identified, and it was shown that this device could be used to monitor an individual patient's response to anti-cancer therapy. Viable tumour-derived epithelial cells (circulating tumour cells or CTCs) have been identified in peripheral blood from cancer patients and are probably the origin of intractable metastatic disease 1 , 2 , 3 , 4 . Although extremely rare, CTCs represent a potential alternative to invasive biopsies as a source of tumour tissue for the detection, characterization and monitoring of non-haematologic cancers 5 , 6 , 7 , 8 . The ability to identify, isolate, propagate and molecularly characterize CTC subpopulations could further the discovery of cancer stem cell biomarkers and expand the understanding of the biology of metastasis. Current strategies for isolating CTCs are limited to complex analytic approaches that generate very low yield and purity 9 . Here we describe the development of a unique microfluidic platform (the ‘CTC-chip’) capable of efficient and selective separation of viable CTCs from peripheral whole blood samples, mediated by the interaction of target CTCs with antibody (EpCAM)-coated microposts under precisely controlled laminar flow conditions, and without requisite pre-labelling or processing of samples. The CTC-chip successfully identified CTCs in the peripheral blood of patients with metastatic lung, prostate, pancreatic, breast and colon cancer in 115 of 116 (99%) samples, with a range of 5–1,281 CTCs per ml and approximately 50% purity. In addition, CTCs were isolated in 7/7 patients with early-stage prostate cancer. Given the high sensitivity and specificity of the CTC-chip, we tested its potential utility in monitoring response to anti-cancer therapy. In a small cohort of patients with metastatic cancer undergoing systemic treatment, temporal changes in CTC numbers correlated reasonably well with the clinical course of disease as measured by standard radiographic methods. Thus, the CTC-chip provides a new and effective tool for accurate identification and measurement of CTCs in patients with cancer. It has broad implications in advancing both cancer biology research and clinical cancer management, including the detection, diagnosis and monitoring of cancer 10 .
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23 These authors contributed equally to this paper. Present addresses: National Human Genome Research Institute/NIH Cancer Genetics Branch, Bethesda, Maryland 20892, USA (D.W.B.); Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan 48109, USA (U.J.B.).
ISSN:	0028-0836 1476-4687 1476-4687 1476-4679
DOI:	10.1038/nature06385