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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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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