Cell Reports (Jan 2014)
High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance Factor
- 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
Affiliations
- Justin D. Lathia
- Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA
- Meizhang Li
- Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA
- Maksim Sinyuk
- Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA
- Alvaro G. Alvarado
- Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA
- William A. Flavahan
- Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA
- Kevin Stoltz
- Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA
- Ann Mari Rosager
- Department of Pathology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense 5000, Denmark
- James Hale
- Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA
- Masahiro Hitomi
- Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA
- Joseph Gallagher
- Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA
- Qiulian Wu
- Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA
- Jody Martin
- BD Biosciences, La Jolla, CA 92037, USA
- Jason G. Vidal
- BD Biosciences, La Jolla, CA 92037, USA
- Ichiro Nakano
- Department of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
- Rikke H. Dahlrot
- Department of Oncology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense 5000, Denmark
- Steinbjørn Hansen
- Department of Oncology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense 5000, Denmark
- Roger E. McLendon
- Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
- Andrew E. Sloan
- Case Comprehensive Cancer Center, Cleveland, OH 44106, USA
- Shideng Bao
- Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA
- Anita B. Hjelmeland
- Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA
- Christian T. Carson
- BD Biosciences, La Jolla, CA 92037, USA
- Ulhas P. Naik
- Department of Biology, University of Delaware, Newark, DE 19716, USA
- Bjarne Kristensen
- Department of Pathology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense 5000, Denmark
- Jeremy N. Rich
- Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA
- DOI
- https://doi.org/10.1016/j.celrep.2013.11.043
- Journal volume & issue
-
Vol. 6,
no. 1
pp. 117 – 129
Abstract
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.
