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A microfluidic device for label-free, physical capture of circulating tumor cell-clusters
Cancer cells metastasize through the bloodstream either as single migratory circulating tumor cells (CTCs) or as multicellular groupings (CTC-clusters). Existing technologies for CTC enrichment are designed primarily to isolate single CTCs, and while CTC-clusters are detectable in some cases, their...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490017/ https://www.ncbi.nlm.nih.gov/pubmed/25984697 http://dx.doi.org/10.1038/nmeth.3404 |
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author | Sarioglu, A. Fatih Aceto, Nicola Kojic, Nikola Donaldson, Maria C. Zeinali, Mahnaz Hamza, Bashar Engstrom, Amanda Zhu, Huili Sundaresan, Tilak K. Miyamoto, David T. Luo, Xi Bardia, Aditya Wittner, Ben S. Ramaswamy, Sridhar Shioda, Toshi Ting, David T. Stott, Shannon L. Kapur, Ravi Maheswaran, Shyamala Haber, Daniel A. Toner, Mehmet |
author_facet | Sarioglu, A. Fatih Aceto, Nicola Kojic, Nikola Donaldson, Maria C. Zeinali, Mahnaz Hamza, Bashar Engstrom, Amanda Zhu, Huili Sundaresan, Tilak K. Miyamoto, David T. Luo, Xi Bardia, Aditya Wittner, Ben S. Ramaswamy, Sridhar Shioda, Toshi Ting, David T. Stott, Shannon L. Kapur, Ravi Maheswaran, Shyamala Haber, Daniel A. Toner, Mehmet |
author_sort | Sarioglu, A. Fatih |
collection | PubMed |
description | Cancer cells metastasize through the bloodstream either as single migratory circulating tumor cells (CTCs) or as multicellular groupings (CTC-clusters). Existing technologies for CTC enrichment are designed primarily to isolate single CTCs, and while CTC-clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here, we developed a microchip technology (Cluster-Chip) specifically designed to capture CTC-clusters independent of tumor-specific markers from unprocessed blood. CTC-clusters are isolated through specialized bifurcating traps under low shear-stress conditions that preserve their integrity and even two-cell clusters are captured efficiently. Using the Cluster-Chip, we identify CTC-clusters in 30–40% of patients with metastatic cancers of the breast, prostate and melanoma. RNA sequencing of CTC-clusters confirms their tumor origin and identifies leukocytes within the clusters as tissue-derived macrophages. Together, the development of a device for efficient capture of CTC-clusters will enable detailed characterization of their biological properties and role in cancer metastasis. |
format | Online Article Text |
id | pubmed-4490017 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-44900172016-01-01 A microfluidic device for label-free, physical capture of circulating tumor cell-clusters Sarioglu, A. Fatih Aceto, Nicola Kojic, Nikola Donaldson, Maria C. Zeinali, Mahnaz Hamza, Bashar Engstrom, Amanda Zhu, Huili Sundaresan, Tilak K. Miyamoto, David T. Luo, Xi Bardia, Aditya Wittner, Ben S. Ramaswamy, Sridhar Shioda, Toshi Ting, David T. Stott, Shannon L. Kapur, Ravi Maheswaran, Shyamala Haber, Daniel A. Toner, Mehmet Nat Methods Article Cancer cells metastasize through the bloodstream either as single migratory circulating tumor cells (CTCs) or as multicellular groupings (CTC-clusters). Existing technologies for CTC enrichment are designed primarily to isolate single CTCs, and while CTC-clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here, we developed a microchip technology (Cluster-Chip) specifically designed to capture CTC-clusters independent of tumor-specific markers from unprocessed blood. CTC-clusters are isolated through specialized bifurcating traps under low shear-stress conditions that preserve their integrity and even two-cell clusters are captured efficiently. Using the Cluster-Chip, we identify CTC-clusters in 30–40% of patients with metastatic cancers of the breast, prostate and melanoma. RNA sequencing of CTC-clusters confirms their tumor origin and identifies leukocytes within the clusters as tissue-derived macrophages. Together, the development of a device for efficient capture of CTC-clusters will enable detailed characterization of their biological properties and role in cancer metastasis. 2015-05-18 2015-07 /pmc/articles/PMC4490017/ /pubmed/25984697 http://dx.doi.org/10.1038/nmeth.3404 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Sarioglu, A. Fatih Aceto, Nicola Kojic, Nikola Donaldson, Maria C. Zeinali, Mahnaz Hamza, Bashar Engstrom, Amanda Zhu, Huili Sundaresan, Tilak K. Miyamoto, David T. Luo, Xi Bardia, Aditya Wittner, Ben S. Ramaswamy, Sridhar Shioda, Toshi Ting, David T. Stott, Shannon L. Kapur, Ravi Maheswaran, Shyamala Haber, Daniel A. Toner, Mehmet A microfluidic device for label-free, physical capture of circulating tumor cell-clusters |
title | A microfluidic device for label-free, physical capture of circulating tumor cell-clusters |
title_full | A microfluidic device for label-free, physical capture of circulating tumor cell-clusters |
title_fullStr | A microfluidic device for label-free, physical capture of circulating tumor cell-clusters |
title_full_unstemmed | A microfluidic device for label-free, physical capture of circulating tumor cell-clusters |
title_short | A microfluidic device for label-free, physical capture of circulating tumor cell-clusters |
title_sort | microfluidic device for label-free, physical capture of circulating tumor cell-clusters |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490017/ https://www.ncbi.nlm.nih.gov/pubmed/25984697 http://dx.doi.org/10.1038/nmeth.3404 |
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