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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

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JournalGenome biology
DatePublished - 20 May 2008
Issue number5
Volume9
Number of pages13
Pages (from-to)1-13
Original languageEnglish

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.

    Research areas

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

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