Abstract:
:Controversy remains over whether the cancer stem cell (CSC) theory applies to all tumors. To determine whether cells within a highly aggressive solid tumor are stochastically or hierarchically organized, we combined a reporter system where the nucleostemin (NS) promoter drives GFP expression (termed NS-GFP) with a mouse brain tumor model induced by retroviral Ras expression on a p16(Ink4a)/p19(Arf)-deficient background. The NS-GFP system allowed us to monitor the differentiation process of normal neural stem/precursor cells by analyzing GFP fluorescence intensity. In tumor-bearing mice, despite the very high frequency of tumorigenic cells, we successfully identified the NS-GFP(+) cells as tumor-initiating cells (T-ICs). The clonal studies conclusively established that phenotypical heterogeneity can exist among the cells comprising a genetically homogeneous tumor, suggesting that this aggressive brain tumor follows the CSC model. Detailed analyses of the NS-GFP(+) brain tumor cells revealed that T-ICs showed activation of the receptor tyrosine kinase c-Met, which functions in tumor invasiveness. Thus, the NS-GFP system provides a powerful tool to elucidate stem cell biology in normal and malignant tissues.
journal_name
Proc Natl Acad Sci U S Aauthors
Tamase A,Muraguchi T,Naka K,Tanaka S,Kinoshita M,Hoshii T,Ohmura M,Shugo H,Ooshio T,Nakada M,Sawamoto K,Onodera M,Matsumoto K,Oshima M,Asano M,Saya H,Okano H,Suda T,Hamada J,Hirao Adoi
10.1073/pnas.0905016106subject
Has Abstractpub_date
2009-10-06 00:00:00pages
17163-8issue
40eissn
0027-8424issn
1091-6490pii
0905016106journal_volume
106pub_type
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