A Flexible Reporter System for Direct Observation and Isolation of Cancer Stem Cells

Summary: Many tumors are hierarchically organized with a minority cell population that has stem-like properties and enhanced ability to initiate tumorigenesis and drive therapeutic relapse. These cancer stem cells (CSCs) are typically identified by complex combinations of cell-surface markers that d...

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Main Authors: Binwu Tang, Asaf Raviv, Dominic Esposito, Kathleen C. Flanders, Catherine Daniel, Bao Tram Nghiem, Susan Garfield, Langston Lim, Poonam Mannan, Ana I. Robles, William I. Smith, Jr., Joshua Zimmerberg, Rea Ravin, Lalage M. Wakefield
Format: Article
Language:English
Published: Elsevier 2015-01-01
Series:Stem Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S221367111400352X
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spelling doaj-3bc670f3127f45a59cc7a7001fdd4b3d2020-11-24T22:02:34ZengElsevierStem Cell Reports2213-67112015-01-0141155169A Flexible Reporter System for Direct Observation and Isolation of Cancer Stem CellsBinwu Tang0Asaf Raviv1Dominic Esposito2Kathleen C. Flanders3Catherine Daniel4Bao Tram Nghiem5Susan Garfield6Langston Lim7Poonam Mannan8Ana I. Robles9William I. Smith, Jr.10Joshua Zimmerberg11Rea Ravin12Lalage M. Wakefield13Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, MD 20892, USALaboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, MD 20892, USAProtein Expression Laboratory, Advanced Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USALaboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, MD 20892, USALaboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, MD 20892, USALaboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, MD 20892, USAConfocal Microscopy Core, National Cancer Institute, Bethesda, MD 20892, USAConfocal Microscopy Core, National Cancer Institute, Bethesda, MD 20892, USAConfocal Microscopy Core, National Cancer Institute, Bethesda, MD 20892, USALaboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892 USADepartment of Pathology, Suburban Hospital, Bethesda, MD 20814, USAProgram in Physical Biology, National Institute of Child Health and Human Development, Bethesda, MD 20892, USAProgram in Physical Biology, National Institute of Child Health and Human Development, Bethesda, MD 20892, USALaboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA; Corresponding authorSummary: Many tumors are hierarchically organized with a minority cell population that has stem-like properties and enhanced ability to initiate tumorigenesis and drive therapeutic relapse. These cancer stem cells (CSCs) are typically identified by complex combinations of cell-surface markers that differ among tumor types. Here, we developed a flexible lentiviral-based reporter system that allows direct visualization of CSCs based on functional properties. The reporter responds to the core stem cell transcription factors OCT4 and SOX2, with further selectivity and kinetic resolution coming from use of a proteasome-targeting degron. Cancer cells marked by this reporter have the expected properties of self-renewal, generation of heterogeneous offspring, high tumor- and metastasis-initiating activity, and resistance to chemotherapeutics. With this approach, the spatial distribution of CSCs can be assessed in settings that retain microenvironmental and structural cues, and CSC plasticity and response to therapeutics can be monitored in real time. : In this article, Wakefield and colleagues show that a subpopulation of cancer cells with characteristics of cancer stem cells can be identified and visualized in vitro and in vivo using a lentiviral-based fluorescent reporter that responds to the presence of the stemness master transcription factors SOX2 and OCT4.http://www.sciencedirect.com/science/article/pii/S221367111400352X
collection DOAJ
language English
format Article
sources DOAJ
author Binwu Tang
Asaf Raviv
Dominic Esposito
Kathleen C. Flanders
Catherine Daniel
Bao Tram Nghiem
Susan Garfield
Langston Lim
Poonam Mannan
Ana I. Robles
William I. Smith, Jr.
Joshua Zimmerberg
Rea Ravin
Lalage M. Wakefield
spellingShingle Binwu Tang
Asaf Raviv
Dominic Esposito
Kathleen C. Flanders
Catherine Daniel
Bao Tram Nghiem
Susan Garfield
Langston Lim
Poonam Mannan
Ana I. Robles
William I. Smith, Jr.
Joshua Zimmerberg
Rea Ravin
Lalage M. Wakefield
A Flexible Reporter System for Direct Observation and Isolation of Cancer Stem Cells
Stem Cell Reports
author_facet Binwu Tang
Asaf Raviv
Dominic Esposito
Kathleen C. Flanders
Catherine Daniel
Bao Tram Nghiem
Susan Garfield
Langston Lim
Poonam Mannan
Ana I. Robles
William I. Smith, Jr.
Joshua Zimmerberg
Rea Ravin
Lalage M. Wakefield
author_sort Binwu Tang
title A Flexible Reporter System for Direct Observation and Isolation of Cancer Stem Cells
title_short A Flexible Reporter System for Direct Observation and Isolation of Cancer Stem Cells
title_full A Flexible Reporter System for Direct Observation and Isolation of Cancer Stem Cells
title_fullStr A Flexible Reporter System for Direct Observation and Isolation of Cancer Stem Cells
title_full_unstemmed A Flexible Reporter System for Direct Observation and Isolation of Cancer Stem Cells
title_sort flexible reporter system for direct observation and isolation of cancer stem cells
publisher Elsevier
series Stem Cell Reports
issn 2213-6711
publishDate 2015-01-01
description Summary: Many tumors are hierarchically organized with a minority cell population that has stem-like properties and enhanced ability to initiate tumorigenesis and drive therapeutic relapse. These cancer stem cells (CSCs) are typically identified by complex combinations of cell-surface markers that differ among tumor types. Here, we developed a flexible lentiviral-based reporter system that allows direct visualization of CSCs based on functional properties. The reporter responds to the core stem cell transcription factors OCT4 and SOX2, with further selectivity and kinetic resolution coming from use of a proteasome-targeting degron. Cancer cells marked by this reporter have the expected properties of self-renewal, generation of heterogeneous offspring, high tumor- and metastasis-initiating activity, and resistance to chemotherapeutics. With this approach, the spatial distribution of CSCs can be assessed in settings that retain microenvironmental and structural cues, and CSC plasticity and response to therapeutics can be monitored in real time. : In this article, Wakefield and colleagues show that a subpopulation of cancer cells with characteristics of cancer stem cells can be identified and visualized in vitro and in vivo using a lentiviral-based fluorescent reporter that responds to the presence of the stemness master transcription factors SOX2 and OCT4.
url http://www.sciencedirect.com/science/article/pii/S221367111400352X
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