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Characterization of sphere-forming cells with stem-like properties from the small cell lung cancer cell line H446.
MedLine Citation:
PMID:  22521544     Owner:  NLM     Status:  Publisher    
A relatively novel paradigm in tumor biology hypothesizes that cancer growth is driven by tumor cells with stem-like properties. However, direct proof of a population of stem cells in small cell lung cancer (SCLC) remains elusive. In this study, we enriched for stem-like cells from the SCLC cell line H446 by growing them as spheres in a defined serum-free medium. Sphere-derived cells have increased in vitro clonogenic and in vivo tumorigenic potentials as well as drug-resistant properties. After enrichment for stem-like cells, we used multiple candidate stem cell markers to examine the expression profile and found that the sphere-derived cells contained a higher proportion of cells expressing the stem cell surface markers uPAR and CD133 when compared with parental cells. To identify a selectable marker for the sphere-forming cells, we evaluated the sphere-forming abilities of uPAR(+) and uPAR(-) cells as well as the sphere-forming abilities of CD133(+) and CD133(-) cells. Both CD133(+) and CD133(-) cell fractions were capable of forming spheres, and no statistically significant difference was observed in the sphere-forming efficiency between these two populations. In contrast, cells derived from the uPAR(+) fraction were capable of forming spheres, whereas cells derived from the uPAR(-) fraction remained as single cells. Moreover, uPAR(+) cells efficiently formed transplantable tumors, whereas uPAR(-) cells were unable to initiate tumors when transplanted at equivalent cell numbers. In addition, uPAR(+) cells could differentiate into CD56(+) cells, CK(+) cells, and uPAR(-) cells. These data support the existence of a population of tumor sphere-forming cells with stem cell properties in the H446 SCLC cell line. Furthermore, the stem cell population may be enriched in cells expressing the uPAR cell surface marker.
Xiaofei Qiu; Zhengyan Wang; Yanlei Li; Yajing Miao; Yu Ren; Yajing Luan
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-17
Journal Detail:
Title:  Cancer letters     Volume:  -     ISSN:  1872-7980     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ireland Ltd.
Department of Pathology, Tianjin Medical University, Tianjin, China.
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