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

Richard Birnie1, Steven D Bryce2, Claire Roome3, Vincent Dussupt1, Alastair Droop4, Shona H Lang2, Paul A Berry2, Catherine F Hyde2, John L Lewis2, Michael J Stower5, Norman J Maitland2 and Anne T Collins2*

Author Affiliations

1 Pro-Cure Therapeutics Ltd, The Biocentre, Innovation Way, York Science Park, Heslington, York YO10 5NY, UK

2 YCR Cancer Research Unit, Department of Biology, University of York, York YO10 5YW, UK

3 Hull York Medical School, University of York, Heslington, York YO10 5DD, UK

4 York Centre for Complex Systems Analysis, Department of Biology, University of York, York YO10 5YW, UK

5 Department of Urology, York Hospital, Wigginton Road, York YO31 8HE, UK

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Genome Biology 2008, 9:R83  doi:10.1186/gb-2008-9-5-r83

Published: 20 May 2008

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+2β1hi phenotype have the properties of prostate cancer stem cells. We have compared gene expression in these cells relative to their normal and differentiated (CD133-2β1low) 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 κB (NF-κB), revealed preferential targeting of the cancer stem cell and progenitor population for apoptosis whilst sparing normal stem cells. NF-κB 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.