Cargando…

Discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule

Circulating tumor cells consist of phenotypically distinct subpopulations that originate from the tumor microenvironment. We report a circulating tumor cell dual selection assay that uses discrete microfluidics to select circulating tumor cell subpopulations from a single blood sample; circulating t...

Descripción completa

Detalles Bibliográficos
Autores principales: Witek, Małgorzata A., Aufforth, Rachel D., Wang, Hong, Kamande, Joyce W., Jackson, Joshua M., Pullagurla, Swathi R., Hupert, Mateusz L., Usary, Jerry, Wysham, Weiya Z., Hilliard, Dawud, Montgomery, Stephanie, Bae-Jump, Victoria, Carey, Lisa A., Gehrig, Paola A., Milowsky, Matthew I., Perou, Charles M., Soper, John T., Whang, Young E., Yeh, Jen Jen, Martin, George, Soper, Steven A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871807/
https://www.ncbi.nlm.nih.gov/pubmed/29657983
http://dx.doi.org/10.1038/s41698-017-0028-8
_version_ 1783309701305335808
author Witek, Małgorzata A.
Aufforth, Rachel D.
Wang, Hong
Kamande, Joyce W.
Jackson, Joshua M.
Pullagurla, Swathi R.
Hupert, Mateusz L.
Usary, Jerry
Wysham, Weiya Z.
Hilliard, Dawud
Montgomery, Stephanie
Bae-Jump, Victoria
Carey, Lisa A.
Gehrig, Paola A.
Milowsky, Matthew I.
Perou, Charles M.
Soper, John T.
Whang, Young E.
Yeh, Jen Jen
Martin, George
Soper, Steven A.
author_facet Witek, Małgorzata A.
Aufforth, Rachel D.
Wang, Hong
Kamande, Joyce W.
Jackson, Joshua M.
Pullagurla, Swathi R.
Hupert, Mateusz L.
Usary, Jerry
Wysham, Weiya Z.
Hilliard, Dawud
Montgomery, Stephanie
Bae-Jump, Victoria
Carey, Lisa A.
Gehrig, Paola A.
Milowsky, Matthew I.
Perou, Charles M.
Soper, John T.
Whang, Young E.
Yeh, Jen Jen
Martin, George
Soper, Steven A.
author_sort Witek, Małgorzata A.
collection PubMed
description Circulating tumor cells consist of phenotypically distinct subpopulations that originate from the tumor microenvironment. We report a circulating tumor cell dual selection assay that uses discrete microfluidics to select circulating tumor cell subpopulations from a single blood sample; circulating tumor cells expressing the established marker epithelial cell adhesion molecule and a new marker, fibroblast activation protein alpha, were evaluated. Both circulating tumor cell subpopulations were detected in metastatic ovarian, colorectal, prostate, breast, and pancreatic cancer patients and 90% of the isolated circulating tumor cells did not co-express both antigens. Clinical sensitivities of 100% showed substantial improvement compared to epithelial cell adhesion molecule selection alone. Owing to high purity (>80%) of the selected circulating tumor cells, molecular analysis of both circulating tumor cell subpopulations was carried out in bulk, including next generation sequencing, mutation analysis, and gene expression. Results suggested fibroblast activation protein alpha and epithelial cell adhesion molecule circulating tumor cells are distinct subpopulations and the use of these in concert can provide information needed to navigate through cancer disease management challenges.
format Online
Article
Text
id pubmed-5871807
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-58718072018-04-11 Discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule Witek, Małgorzata A. Aufforth, Rachel D. Wang, Hong Kamande, Joyce W. Jackson, Joshua M. Pullagurla, Swathi R. Hupert, Mateusz L. Usary, Jerry Wysham, Weiya Z. Hilliard, Dawud Montgomery, Stephanie Bae-Jump, Victoria Carey, Lisa A. Gehrig, Paola A. Milowsky, Matthew I. Perou, Charles M. Soper, John T. Whang, Young E. Yeh, Jen Jen Martin, George Soper, Steven A. NPJ Precis Oncol Article Circulating tumor cells consist of phenotypically distinct subpopulations that originate from the tumor microenvironment. We report a circulating tumor cell dual selection assay that uses discrete microfluidics to select circulating tumor cell subpopulations from a single blood sample; circulating tumor cells expressing the established marker epithelial cell adhesion molecule and a new marker, fibroblast activation protein alpha, were evaluated. Both circulating tumor cell subpopulations were detected in metastatic ovarian, colorectal, prostate, breast, and pancreatic cancer patients and 90% of the isolated circulating tumor cells did not co-express both antigens. Clinical sensitivities of 100% showed substantial improvement compared to epithelial cell adhesion molecule selection alone. Owing to high purity (>80%) of the selected circulating tumor cells, molecular analysis of both circulating tumor cell subpopulations was carried out in bulk, including next generation sequencing, mutation analysis, and gene expression. Results suggested fibroblast activation protein alpha and epithelial cell adhesion molecule circulating tumor cells are distinct subpopulations and the use of these in concert can provide information needed to navigate through cancer disease management challenges. Nature Publishing Group UK 2017-07-25 /pmc/articles/PMC5871807/ /pubmed/29657983 http://dx.doi.org/10.1038/s41698-017-0028-8 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Witek, Małgorzata A.
Aufforth, Rachel D.
Wang, Hong
Kamande, Joyce W.
Jackson, Joshua M.
Pullagurla, Swathi R.
Hupert, Mateusz L.
Usary, Jerry
Wysham, Weiya Z.
Hilliard, Dawud
Montgomery, Stephanie
Bae-Jump, Victoria
Carey, Lisa A.
Gehrig, Paola A.
Milowsky, Matthew I.
Perou, Charles M.
Soper, John T.
Whang, Young E.
Yeh, Jen Jen
Martin, George
Soper, Steven A.
Discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule
title Discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule
title_full Discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule
title_fullStr Discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule
title_full_unstemmed Discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule
title_short Discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule
title_sort discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871807/
https://www.ncbi.nlm.nih.gov/pubmed/29657983
http://dx.doi.org/10.1038/s41698-017-0028-8
work_keys_str_mv AT witekmałgorzataa discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT aufforthracheld discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT wanghong discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT kamandejoycew discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT jacksonjoshuam discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT pullagurlaswathir discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT hupertmateuszl discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT usaryjerry discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT wyshamweiyaz discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT hilliarddawud discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT montgomerystephanie discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT baejumpvictoria discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT careylisaa discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT gehrigpaolaa discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT milowskymatthewi discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT peroucharlesm discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT soperjohnt discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT whangyounge discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT yehjenjen discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT martingeorge discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule
AT soperstevena discretemicrofluidicsfortheisolationofcirculatingtumorcellsubpopulationstargetingfibroblastactivationproteinalphaandepithelialcelladhesionmolecule