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

doi:10.1016/j.celrep.2013.11.043

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 HjelmelandChristian T Carson, Ulhas P Naik, Bjarne Kristensen, Jeremy N Rich

Research output: Contribution to journal › Journal article › Research › peer-review

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.

Original language	English
Journal	Cell Reports
Volume	6
Issue number	1
Pages (from-to)	117-129
DOIs	https://doi.org/10.1016/j.celrep.2013.11.043
Publication status	Published - 24. Dec 2014

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Lathia, J. D., Li, M., Sinyuk, M., Alvarado, A. G., Flavahan, W. A., Stoltz, K., Rosager, A. M., Hale, J., Hitomi, M., Gallagher, J., Wu, Q., Martin, J., Vidal, J. G., Nakano, I., Dahlrot, R. H., Hansen, S., McLendon, R. E., Sloan, A. E., Bao, S., ... Rich, J. N. (2014). High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance Factor. Cell Reports, 6(1), 117-129. https://doi.org/10.1016/j.celrep.2013.11.043

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title = "High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance Factor",

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.",

author = "Lathia, {Justin D} and Meizhang Li and Maksim Sinyuk and Alvarado, {Alvaro G} and Flavahan, {William A} and Kevin Stoltz and Rosager, {Ann Mari} and James Hale and Masahiro Hitomi and Joseph Gallagher and Qiulian Wu and Jody Martin and Vidal, {Jason G} and Ichiro Nakano and Dahlrot, {Rikke H} and Steinbj{\o}rn Hansen and McLendon, {Roger E} and Sloan, {Andrew E} and Shideng Bao and Hjelmeland, {Anita B} and Carson, {Christian T} and Naik, {Ulhas P} and Bjarne Kristensen and Rich, {Jeremy N}",

year = "2014",

month = dec,

day = "24",

doi = "10.1016/j.celrep.2013.11.043",

language = "English",

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pages = "117--129",

journal = "Cell Reports",

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Lathia, JD, Li, M, Sinyuk, M, Alvarado, AG, Flavahan, WA, Stoltz, K, Rosager, AM, Hale, J, Hitomi, M, Gallagher, J, Wu, Q, Martin, J, Vidal, JG, Nakano, I, Dahlrot, RH , Hansen, S, McLendon, RE, Sloan, AE, Bao, S, Hjelmeland, AB, Carson, CT, Naik, UP, Kristensen, B & Rich, JN 2014, 'High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance Factor', Cell Reports, vol. 6, no. 1, pp. 117-129. https://doi.org/10.1016/j.celrep.2013.11.043

TY - JOUR

T1 - High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance Factor

AU - Lathia, Justin D

AU - Li, Meizhang

AU - Sinyuk, Maksim

AU - Alvarado, Alvaro G

AU - Flavahan, William A

AU - Stoltz, Kevin

AU - Rosager, Ann Mari

AU - Hale, James

AU - Hitomi, Masahiro

AU - Gallagher, Joseph

AU - Wu, Qiulian

AU - Martin, Jody

AU - Vidal, Jason G

AU - Nakano, Ichiro

AU - Dahlrot, Rikke H

AU - Hansen, Steinbjørn

AU - McLendon, Roger E

AU - Sloan, Andrew E

AU - Bao, Shideng

AU - Hjelmeland, Anita B

AU - Carson, Christian T

AU - Naik, Ulhas P

AU - Kristensen, Bjarne

AU - Rich, Jeremy N

PY - 2014/12/24

Y1 - 2014/12/24

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2013.11.043

DO - 10.1016/j.celrep.2013.11.043

M3 - Journal article

C2 - 24373972

VL - 6

SP - 117

EP - 129

JO - Cell Reports

JF - Cell Reports

IS - 1

ER -

High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance Factor

Abstract

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