High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance Factor
Stem cells reside in niches that regulate the balance between self-renewal and differentiation. The identity of a stem cell is linked with the ability to interact with its niche through adhesion mechanisms. To identify targets that disrupt cancer stem cell (CSC) adhesion, we performed a flow cytomet...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-01-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713007274 |
| _version_ | 1811283478270967808 |
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| author | Justin D. Lathia Meizhang Li Maksim Sinyuk Alvaro G. Alvarado William A. Flavahan Kevin Stoltz Ann Mari Rosager James Hale Masahiro Hitomi Joseph Gallagher Qiulian Wu Jody Martin Jason G. Vidal Ichiro Nakano Rikke H. Dahlrot Steinbjørn Hansen Roger E. McLendon Andrew E. Sloan Shideng Bao Anita B. Hjelmeland Christian T. Carson Ulhas P. Naik Bjarne Kristensen Jeremy N. Rich |
| author_facet | Justin D. Lathia Meizhang Li Maksim Sinyuk Alvaro G. Alvarado William A. Flavahan Kevin Stoltz Ann Mari Rosager James Hale Masahiro Hitomi Joseph Gallagher Qiulian Wu Jody Martin Jason G. Vidal Ichiro Nakano Rikke H. Dahlrot Steinbjørn Hansen Roger E. McLendon Andrew E. Sloan Shideng Bao Anita B. Hjelmeland Christian T. Carson Ulhas P. Naik Bjarne Kristensen Jeremy N. Rich |
| author_sort | Justin D. Lathia |
| collection | DOAJ |
| description | Stem cells reside in niches that regulate the balance between self-renewal and differentiation. The identity of a stem cell is linked with the ability to interact with its niche through adhesion mechanisms. To identify targets that disrupt cancer stem cell (CSC) adhesion, we performed a flow cytometry screen on patient-derived glioblastoma (GBM) cells and identified junctional adhesion molecule A (JAM-A) as a CSC adhesion mechanism essential for self-renewal and tumor growth. JAM-A was dispensable for normal neural stem/progenitor cell (NPC) function, and JAM-A expression was reduced in normal brain versus GBM. Targeting JAM-A compromised the self-renewal of CSCs. JAM-A expression negatively correlated to GBM patient prognosis. Our results demonstrate that GBM-targeting strategies can be identified through screening adhesion receptors and JAM-A represents a mechanism for niche-driven CSC maintenance. |
| first_indexed | 2024-04-13T02:12:19Z |
| format | Article |
| id | doaj.art-1a5b47c77ca3454db06e203949d37170 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T02:12:19Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-1a5b47c77ca3454db06e203949d371702022-12-22T03:07:14ZengElsevierCell Reports2211-12472014-01-016111712910.1016/j.celrep.2013.11.043High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance FactorJustin D. Lathia0Meizhang Li1Maksim Sinyuk2Alvaro G. Alvarado3William A. Flavahan4Kevin Stoltz5Ann Mari Rosager6James Hale7Masahiro Hitomi8Joseph Gallagher9Qiulian Wu10Jody Martin11Jason G. Vidal12Ichiro Nakano13Rikke H. Dahlrot14Steinbjørn Hansen15Roger E. McLendon16Andrew E. Sloan17Shideng Bao18Anita B. Hjelmeland19Christian T. Carson20Ulhas P. Naik21Bjarne Kristensen22Jeremy N. Rich23Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USADepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USADepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USADepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USADepartment of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USADepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USADepartment of Pathology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense 5000, DenmarkDepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USADepartment of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USADepartment of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USADepartment of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USABD Biosciences, La Jolla, CA 92037, USABD Biosciences, La Jolla, CA 92037, USADepartment of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USADepartment of Oncology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense 5000, DenmarkDepartment of Oncology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense 5000, DenmarkDepartment of Pathology, Duke University Medical Center, Durham, NC 27710, USACase Comprehensive Cancer Center, Cleveland, OH 44106, USADepartment of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USADepartment of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USABD Biosciences, La Jolla, CA 92037, USADepartment of Biology, University of Delaware, Newark, DE 19716, USADepartment of Pathology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense 5000, DenmarkDepartment of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USAStem cells reside in niches that regulate the balance between self-renewal and differentiation. The identity of a stem cell is linked with the ability to interact with its niche through adhesion mechanisms. To identify targets that disrupt cancer stem cell (CSC) adhesion, we performed a flow cytometry screen on patient-derived glioblastoma (GBM) cells and identified junctional adhesion molecule A (JAM-A) as a CSC adhesion mechanism essential for self-renewal and tumor growth. JAM-A was dispensable for normal neural stem/progenitor cell (NPC) function, and JAM-A expression was reduced in normal brain versus GBM. Targeting JAM-A compromised the self-renewal of CSCs. JAM-A expression negatively correlated to GBM patient prognosis. Our results demonstrate that GBM-targeting strategies can be identified through screening adhesion receptors and JAM-A represents a mechanism for niche-driven CSC maintenance.http://www.sciencedirect.com/science/article/pii/S2211124713007274 |
| spellingShingle | Justin D. Lathia Meizhang Li Maksim Sinyuk Alvaro G. Alvarado William A. Flavahan Kevin Stoltz Ann Mari Rosager James Hale Masahiro Hitomi Joseph Gallagher Qiulian Wu Jody Martin Jason G. Vidal Ichiro Nakano Rikke H. Dahlrot Steinbjørn Hansen Roger E. McLendon Andrew E. Sloan Shideng Bao Anita B. Hjelmeland Christian T. Carson Ulhas P. Naik Bjarne Kristensen Jeremy N. Rich High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance Factor Cell Reports |
| title | High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance Factor |
| title_full | High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance Factor |
| title_fullStr | High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance Factor |
| title_full_unstemmed | High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance Factor |
| title_short | High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance Factor |
| title_sort | high throughput flow cytometry screening reveals a role for junctional adhesion molecule a as a cancer stem cell maintenance factor |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713007274 |
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