Gene expression profiling of human prostate cancer stem cells reveals a pro-inflammatory phenotype and the importance of extracellular matrix interactions

Richard Birnie; Steven D. Bryce; Claire Roome; Vincent Dussupt; Alastair Droop; Shona H. Lang; Paul A. Berry; Catherine F. Hyde; John L. Lewis; Michael J. Stower; Norman J. Maitland; Anne T. Collins

doi:10.1186/gb-2008-9-5-r83

Gene expression profiling of human prostate cancer stem cells reveals a pro-inflammatory phenotype and the importance of extracellular matrix interactions

Richard Birnie, Steven D. Bryce, Claire Roome, Vincent Dussupt, Alastair Droop, Shona H. Lang, Paul A. Berry, Catherine F. Hyde, John L. Lewis, Michael J. Stower, Norman J. Maitland, Anne T. Collins

Cancer Research Unit

Research output: Contribution to journal › Article › peer-review

Abstract

Background: The tumor-initiating capacity of many cancers is considered to reside in a small subpopulation of cells (cancer stem cells). We have previously shown that rare prostate epithelial cells with a CD133(+)/alpha(2)beta 1(hi) phenotype have the properties of prostate cancer stem cells. We have compared gene expression in these cells relative to their normal and differentiated (CD133(-)/alpha(2)beta(low)(1)) counterparts, resulting in an informative cancer stem cell gene-expression signature.

Results: Cell cultures were generated from specimens of human prostate cancers (n = 12) and non-malignant control tissues (n = 7). Affymetrix gene-expression arrays were used to analyze total cell RNA from sorted cell populations, and expression changes were selectively validated by quantitative RT-PCR, flow cytometry and immunocytochemistry. Differential expression of multiple genes associated with inflammation, cellular adhesion, and metastasis was observed. Functional studies, using an inhibitor of nuclear factor kappa B (NF-kappa B), revealed preferential targeting of the cancer stem cell and progenitor population for apoptosis whilst sparing normal stem cells. NF-kappa B is a major factor controlling the ability of tumor cells to resist apoptosis and provides an attractive target for new chemopreventative and chemotherapeutic approaches.

Conclusion: We describe an expression signature of 581 genes whose levels are significantly different in prostate cancer stem cells. Functional annotation of this signature identified the JAK-STAT pathway and focal adhesion signaling as key processes in the biology of cancer stem cells.

Original language	English
Article number	R83
Pages (from-to)	1-13
Number of pages	13
Journal	Genome biology
Volume	9
Issue number	5
DOIs	https://doi.org/10.1186/gb-2008-9-5-r83
Publication status	Published - 20 May 2008

Keywords

PLASMA PROTEIN-A
IN-VITRO
PROSPECTIVE IDENTIFICATION
INITIATING CELLS
PROGENITOR CELLS
LEUKEMIA
BIOLOGY
FUSION
GROWTH
ACTIVATION

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10.1186/gb-2008-9-5-r83

http://genomebiology.com/2008/9/5/R83

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Birnie, R., Bryce, S. D., Roome, C., Dussupt, V., Droop, A., Lang, S. H., Berry, P. A., Hyde, C. F., Lewis, J. L., Stower, M. J., Maitland, N. J., & Collins, A. T. (2008). Gene expression profiling of human prostate cancer stem cells reveals a pro-inflammatory phenotype and the importance of extracellular matrix interactions. Genome biology, 9(5), 1-13. Article R83. https://doi.org/10.1186/gb-2008-9-5-r83

@article{171195b97a0b4c85aaba27a5f51b4c7a,

title = "Gene expression profiling of human prostate cancer stem cells reveals a pro-inflammatory phenotype and the importance of extracellular matrix interactions",

abstract = "Background: The tumor-initiating capacity of many cancers is considered to reside in a small subpopulation of cells (cancer stem cells). We have previously shown that rare prostate epithelial cells with a CD133(+)/alpha(2)beta 1(hi) phenotype have the properties of prostate cancer stem cells. We have compared gene expression in these cells relative to their normal and differentiated (CD133(-)/alpha(2)beta(low)(1)) counterparts, resulting in an informative cancer stem cell gene-expression signature.Results: Cell cultures were generated from specimens of human prostate cancers (n = 12) and non-malignant control tissues (n = 7). Affymetrix gene-expression arrays were used to analyze total cell RNA from sorted cell populations, and expression changes were selectively validated by quantitative RT-PCR, flow cytometry and immunocytochemistry. Differential expression of multiple genes associated with inflammation, cellular adhesion, and metastasis was observed. Functional studies, using an inhibitor of nuclear factor kappa B (NF-kappa B), revealed preferential targeting of the cancer stem cell and progenitor population for apoptosis whilst sparing normal stem cells. NF-kappa B is a major factor controlling the ability of tumor cells to resist apoptosis and provides an attractive target for new chemopreventative and chemotherapeutic approaches.Conclusion: We describe an expression signature of 581 genes whose levels are significantly different in prostate cancer stem cells. Functional annotation of this signature identified the JAK-STAT pathway and focal adhesion signaling as key processes in the biology of cancer stem cells.",

keywords = "PLASMA PROTEIN-A, IN-VITRO, PROSPECTIVE IDENTIFICATION, INITIATING CELLS, PROGENITOR CELLS, LEUKEMIA, BIOLOGY, FUSION, GROWTH, ACTIVATION",

author = "Richard Birnie and Bryce, {Steven D.} and Claire Roome and Vincent Dussupt and Alastair Droop and Lang, {Shona H.} and Berry, {Paul A.} and Hyde, {Catherine F.} and Lewis, {John L.} and Stower, {Michael J.} and Maitland, {Norman J.} and Collins, {Anne T.}",

year = "2008",

month = may,

day = "20",

doi = "10.1186/gb-2008-9-5-r83",

language = "English",

volume = "9",

pages = "1--13",

journal = "Genome biology",

issn = "1474-760X",

publisher = "BioMed Central",

number = "5",

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Birnie, R, Bryce, SD, Roome, C, Dussupt, V, Droop, A, Lang, SH, Berry, PA, Hyde, CF, Lewis, JL, Stower, MJ, Maitland, NJ & Collins, AT 2008, 'Gene expression profiling of human prostate cancer stem cells reveals a pro-inflammatory phenotype and the importance of extracellular matrix interactions', Genome biology, vol. 9, no. 5, R83, pp. 1-13. https://doi.org/10.1186/gb-2008-9-5-r83

TY - JOUR

T1 - Gene expression profiling of human prostate cancer stem cells reveals a pro-inflammatory phenotype and the importance of extracellular matrix interactions

AU - Birnie, Richard

AU - Bryce, Steven D.

AU - Roome, Claire

AU - Dussupt, Vincent

AU - Droop, Alastair

AU - Lang, Shona H.

AU - Berry, Paul A.

AU - Hyde, Catherine F.

AU - Lewis, John L.

AU - Stower, Michael J.

AU - Maitland, Norman J.

AU - Collins, Anne T.

PY - 2008/5/20

Y1 - 2008/5/20

N2 - Background: The tumor-initiating capacity of many cancers is considered to reside in a small subpopulation of cells (cancer stem cells). We have previously shown that rare prostate epithelial cells with a CD133(+)/alpha(2)beta 1(hi) phenotype have the properties of prostate cancer stem cells. We have compared gene expression in these cells relative to their normal and differentiated (CD133(-)/alpha(2)beta(low)(1)) counterparts, resulting in an informative cancer stem cell gene-expression signature.Results: Cell cultures were generated from specimens of human prostate cancers (n = 12) and non-malignant control tissues (n = 7). Affymetrix gene-expression arrays were used to analyze total cell RNA from sorted cell populations, and expression changes were selectively validated by quantitative RT-PCR, flow cytometry and immunocytochemistry. Differential expression of multiple genes associated with inflammation, cellular adhesion, and metastasis was observed. Functional studies, using an inhibitor of nuclear factor kappa B (NF-kappa B), revealed preferential targeting of the cancer stem cell and progenitor population for apoptosis whilst sparing normal stem cells. NF-kappa B is a major factor controlling the ability of tumor cells to resist apoptosis and provides an attractive target for new chemopreventative and chemotherapeutic approaches.Conclusion: We describe an expression signature of 581 genes whose levels are significantly different in prostate cancer stem cells. Functional annotation of this signature identified the JAK-STAT pathway and focal adhesion signaling as key processes in the biology of cancer stem cells.

AB - Background: The tumor-initiating capacity of many cancers is considered to reside in a small subpopulation of cells (cancer stem cells). We have previously shown that rare prostate epithelial cells with a CD133(+)/alpha(2)beta 1(hi) phenotype have the properties of prostate cancer stem cells. We have compared gene expression in these cells relative to their normal and differentiated (CD133(-)/alpha(2)beta(low)(1)) counterparts, resulting in an informative cancer stem cell gene-expression signature.Results: Cell cultures were generated from specimens of human prostate cancers (n = 12) and non-malignant control tissues (n = 7). Affymetrix gene-expression arrays were used to analyze total cell RNA from sorted cell populations, and expression changes were selectively validated by quantitative RT-PCR, flow cytometry and immunocytochemistry. Differential expression of multiple genes associated with inflammation, cellular adhesion, and metastasis was observed. Functional studies, using an inhibitor of nuclear factor kappa B (NF-kappa B), revealed preferential targeting of the cancer stem cell and progenitor population for apoptosis whilst sparing normal stem cells. NF-kappa B is a major factor controlling the ability of tumor cells to resist apoptosis and provides an attractive target for new chemopreventative and chemotherapeutic approaches.Conclusion: We describe an expression signature of 581 genes whose levels are significantly different in prostate cancer stem cells. Functional annotation of this signature identified the JAK-STAT pathway and focal adhesion signaling as key processes in the biology of cancer stem cells.

KW - PLASMA PROTEIN-A

KW - IN-VITRO

KW - PROSPECTIVE IDENTIFICATION

KW - INITIATING CELLS

KW - PROGENITOR CELLS

KW - LEUKEMIA

KW - BIOLOGY

KW - FUSION

KW - GROWTH

KW - ACTIVATION

UR - http://www.scopus.com/inward/record.url?scp=47149102561&partnerID=8YFLogxK

U2 - 10.1186/gb-2008-9-5-r83

DO - 10.1186/gb-2008-9-5-r83

M3 - Article

SN - 1474-760X

VL - 9

SP - 1

EP - 13

JO - Genome biology

JF - Genome biology

IS - 5

M1 - R83

ER -

Gene expression profiling of human prostate cancer stem cells reveals a pro-inflammatory phenotype and the importance of extracellular matrix interactions

Abstract

Keywords

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