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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2010-3-31
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pubmed:abstractText |
There is mounting evidence that tumors are initiated by a rare subset of cells called cancer stem cells (CSCs). CSCs are generally quiescent, self-renew, form tumors at low numbers, and give rise to the heterogeneous cell types found within a tumor. CSCs isolated from multiple tumor types differentiate both in vivo and in vitro when cultured in serum, yet the factors responsible for their differentiation have not yet been identified. Here we show that vitronectin is the component of human serum driving stem cell differentiation through an integrin alpha V beta 3-dependent mechanism. CSCs cultured on vitronectin result in downregulation of stem cell genes, modulation of differentiation markers, and loss of beta-catenin nuclear localization. Blocking integrin alpha V beta 3 inhibits differentiation and subsequently tumor formation. Thus, CSCs must be engaged by one or more extracellular signals to differentiate and initiate tumor formation, defining a new axis for future novel therapies aimed at both the extrinsic and intracellular pathways.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1549-4918
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
31
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
390-8
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pubmed:meshHeading |
pubmed-meshheading:19998373-Animals,
pubmed-meshheading:19998373-Biological Markers,
pubmed-meshheading:19998373-Blood Proteins,
pubmed-meshheading:19998373-Breast Neoplasms,
pubmed-meshheading:19998373-Carcinoma,
pubmed-meshheading:19998373-Cell Differentiation,
pubmed-meshheading:19998373-Cell Line, Tumor,
pubmed-meshheading:19998373-Cell Transformation, Neoplastic,
pubmed-meshheading:19998373-Chromatography, Liquid,
pubmed-meshheading:19998373-Female,
pubmed-meshheading:19998373-Gene Expression Regulation,
pubmed-meshheading:19998373-Humans,
pubmed-meshheading:19998373-Integrin alphaVbeta3,
pubmed-meshheading:19998373-Male,
pubmed-meshheading:19998373-Mass Spectrometry,
pubmed-meshheading:19998373-Mice,
pubmed-meshheading:19998373-Neoplasms,
pubmed-meshheading:19998373-Neoplastic Stem Cells,
pubmed-meshheading:19998373-Nuclear Localization Signals,
pubmed-meshheading:19998373-Prostatic Neoplasms,
pubmed-meshheading:19998373-Vitronectin,
pubmed-meshheading:19998373-beta Catenin
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pubmed:year |
2010
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pubmed:articleTitle |
Identification of vitronectin as an extrinsic inducer of cancer stem cell differentiation and tumor formation.
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pubmed:affiliation |
Cancer Stem Cell Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, USA. hurte@ncifcrf.gov
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural,
Research Support, N.I.H., Intramural
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