Source:http://linkedlifedata.com/resource/pubmed/id/16024622
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
14
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pubmed:dateCreated |
2005-7-18
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pubmed:abstractText |
Recently, several human cancers including leukemia and breast and brain tumors were found to contain stem-like cancer cells called cancer stem cells (CSC). Most of these CSCs were identified using markers that identify putative normal stem cells. In some cases, stem-like cancer cells were identified using the flow cytometry-based side population technique. In this study, we first show that approximately 30% of cultured human cancer cells and xenograft tumors examined ( approximately 30 in total) possess a detectable side population. Purified side population cells from two cell lines (U373 glioma and MCF7 breast cancer) and a xenograft prostate tumor (LAPC-9) are more tumorigenic than the corresponding non-side population cells. These side population cells also possess some intrinsic stem cell properties as they generate non-side population cells in vivo, can be further transplanted, and preferentially express some "stemness" genes, including Notch-1 and beta-catenin. Because the side population phenotype is mainly mediated by ABCG2, an ATP-binding cassette half-transporter associated with multidrug resistance, we subsequently studied ABCG2+ and ABCG2- cancer cells with respect to their tumorigenicity in vivo. Although side population cells show increased ABCG2 mRNA expression relative to the non-side population cells and all cancer cells and xenograft tumors examined express ABCG2 in a small fraction (0.5-3%) of the cells, highly purified ABCG2+ cancer cells, surprisingly, have very similar tumorigenicity to the ABCG2- cancer cells. Mechanistic studies indicate that ABCG2 expression is associated with proliferation and ABCG2+ cancer cells can generate ABCG2- cells. However, ABCG2- cancer cells can also generate ABCG2+ cells. Furthermore, the ABCG2- cancer cells form more and larger clones in the long-term clonal analyses and the ABCG2- population preferentially expresses several "stemness" genes. Taken together, our results suggest that (a) the side population is enriched with tumorigenic stem-like cancer cells, (b) ABCG2 expression identifies mainly fast-cycling tumor progenitors, and (c) the ABCG2- population contains primitive stem-like cancer cells.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
65
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6207-19
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:16024622-ATP-Binding Cassette Transporters,
pubmed-meshheading:16024622-Animals,
pubmed-meshheading:16024622-Cell Growth Processes,
pubmed-meshheading:16024622-Cell Line, Tumor,
pubmed-meshheading:16024622-Female,
pubmed-meshheading:16024622-Humans,
pubmed-meshheading:16024622-Male,
pubmed-meshheading:16024622-Mice,
pubmed-meshheading:16024622-Neoplasm Proteins,
pubmed-meshheading:16024622-Neoplasm Transplantation,
pubmed-meshheading:16024622-Neoplasms,
pubmed-meshheading:16024622-Neoplastic Stem Cells,
pubmed-meshheading:16024622-Transplantation, Heterologous
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pubmed:year |
2005
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pubmed:articleTitle |
Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2- cancer cells are similarly tumorigenic.
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pubmed:affiliation |
Department of Carcinogenesis, Science Park-Research Division, The University of Texas M.D. Anderson Cancer Center, Smithville, Texas 78957, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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