PMID- 18268494 OWN - NLM STAT- MEDLINE DCOM- 20080422 LR - 20220408 IS - 0007-0920 (Print) IS - 1532-1827 (Electronic) IS - 0007-0920 (Linking) VI - 98 IP - 4 DP - 2008 Feb 26 TI - CD44+ CD24(-) prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis. PG - 756-65 LID - 10.1038/sj.bjc.6604242 [doi] AB - Recent evidence supports the hypothesis that cancer stem cells are responsible for tumour initiation and formation. Using flow cytometry, we isolated a population of CD44+CD24(-) prostate cells that display stem cell characteristics as well as gene expression patterns that predict overall survival in prostate cancer patients. CD44+CD24(-) cells form colonies in soft agar and form tumours in NOD/SCID mice when as few as 100 cells are injected. Furthermore, CD44+CD24(-) cells express genes known to be important in stem cell maintenance, such as BMI-1 and Oct-3/4. Moreover, we can maintain CD44+CD24(-) prostate stem-like cells as nonadherent spheres in serum-replacement media without substantially shifting gene expression. Addition of serum results in adherence to plastic and shifts gene expression patterns to resemble the differentiated parental cells. Thus, we propose that CD44+CD24(-) prostate cells are stem-like cells responsible for tumour initiation and we provide a genomic definition of these cells and the differentiated cells they give rise to. Furthermore, gene expression patterns of CD44+CD24(-) cells have a genomic signature that is predictive of poor patient prognosis. Therefore, CD44+CD24(-) LNCaP prostate cells offer an attractive model system to both explore the biology important to the maintenance and differentiation of prostate cancer stem cells as well as to develop the therapeutics, as the gene expression pattern in these cells is consistent with poor survival in prostate cancer patients. FAU - Hurt, E M AU - Hurt EM AD - Cancer Stem Cell Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA. hurte@ncifcrf.gov FAU - Kawasaki, B T AU - Kawasaki BT FAU - Klarmann, G J AU - Klarmann GJ FAU - Thomas, S B AU - Thomas SB FAU - Farrar, W L AU - Farrar WL LA - eng GR - N01CO12400/CA/NCI NIH HHS/United States GR - N01-CO-12400/CO/NCI NIH HHS/United States GR - ImNIH/Intramural NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural DEP - 20080212 PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 RN - 0 (Biomarkers, Tumor) RN - 0 (CD24 Antigen) RN - 0 (Hyaluronan Receptors) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Biomarkers, Tumor/genetics/*metabolism MH - CD24 Antigen/*metabolism MH - Flow Cytometry MH - Gene Expression Profiling MH - Humans MH - Hyaluronan Receptors/*metabolism MH - Male MH - Mice MH - Mice, Inbred NOD MH - Mice, SCID MH - *Models, Biological MH - Neoplasm Invasiveness MH - Neoplastic Stem Cells/*metabolism MH - Oligonucleotide Array Sequence Analysis MH - Phenotype MH - Prognosis MH - Prostate/*metabolism/pathology MH - Prostatic Neoplasms/*metabolism/*pathology MH - RNA, Messenger/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Transplantation, Heterologous MH - Tumor Stem Cell Assay PMC - PMC2259168 EDAT- 2008/02/13 09:00 MHDA- 2008/04/23 09:00 PMCR- 2009/02/26 CRDT- 2008/02/13 09:00 PHST- 2008/02/13 09:00 [pubmed] PHST- 2008/04/23 09:00 [medline] PHST- 2008/02/13 09:00 [entrez] PHST- 2009/02/26 00:00 [pmc-release] AID - 6604242 [pii] AID - 10.1038/sj.bjc.6604242 [doi] PST - ppublish SO - Br J Cancer. 2008 Feb 26;98(4):756-65. doi: 10.1038/sj.bjc.6604242. Epub 2008 Feb 12.