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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-05

AUTHORS

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

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+/alpha2beta1hi phenotype have the properties of prostate cancer stem cells. We have compared gene expression in these cells relative to their normal and differentiated (CD133-/alpha2beta1low) 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 kappaB (NF-kappaB), revealed preferential targeting of the cancer stem cell and progenitor population for apoptosis whilst sparing normal stem cells. NF-kappaB 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. More... »

PAGES

r83

References to SciGraph publications

Journal

TITLE

Genome Biology

ISSUE

5

VOLUME

9

Author Affiliations

From Grant

  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/gb-2008-9-5-r83

    DOI

    http://dx.doi.org/10.1186/gb-2008-9-5-r83

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1044588961

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18492237


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