TY - JOUR
T1 - Selection of tumorigenic melanoma cells using ALDH
AU - Boonyaratanakornkit, Jim B.
AU - Yue, Lili
AU - Strachan, Lauren R.
AU - Scalapino, Kenneth J.
AU - Leboit, Philip E.
AU - Lu, Ying
AU - Leong, Stanley P.
AU - Smith, Janellen E.
AU - Ghadially, Ruby
N1 - Funding Information:
This work was supported by an NIH AR01 grant (RG), the Department of Veterans Affairs (RG), as well as gifts from D Gregory, JC McIntosh, and S Reeves. We thank C Largman, A Charruyer, HJ Lawrence, T Jenkins, M Florero, and L-C Liu for invaluable advice and support. We thank S Fong for his outstanding technical support. Dr Scalapino's work is supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development.
PY - 2010/12
Y1 - 2010/12
N2 - Despite increasing knowledge regarding melanoma-initiating cells (MICs), questions persist regarding the number and phenotypic nature of cells with tumor-generating capability. Evidence for a phenotypically distinct human MIC has been found in NOD/SCID (non-obese diabetic/severe combined immunodeficiency) mice. However, a phenotypically distinct human MIC was not found in the NOD/SCIDIl2rg/(NSG) mouse model. The demonstration of a distinct population of human melanoma cells responsible for tumorigenesis and tumor cell self-renewal would provide an important target for new melanoma therapies. In this study, we show a 100-fold range in MIC frequency in human melanoma (1 in 18,000 to 1 in 1,851,000 cells) in the NOD/SCID mouse. In this model, human melanoma cells with high aldehyde dehydrogenase (ALDH) activity were enriched 16.8-fold in tumorigenic cells over unfractionated (UNF) cells, such that 1 in 21,000 cells was a MIC. In the NSG mouse, the ALDH expressing cell population was enriched 100-fold in tumorigenic cells over UNF cells, such that one in four cells was a MIC. Xenograft melanomas that developed from ALDH cells displayed robust self-renewal, whereas those from ALDH cells showed minimal self-renewal in vitro. Thus, ALDH melanoma cells have enhanced tumorigenicity over ALDH cells and superior self-renewal ability.
AB - Despite increasing knowledge regarding melanoma-initiating cells (MICs), questions persist regarding the number and phenotypic nature of cells with tumor-generating capability. Evidence for a phenotypically distinct human MIC has been found in NOD/SCID (non-obese diabetic/severe combined immunodeficiency) mice. However, a phenotypically distinct human MIC was not found in the NOD/SCIDIl2rg/(NSG) mouse model. The demonstration of a distinct population of human melanoma cells responsible for tumorigenesis and tumor cell self-renewal would provide an important target for new melanoma therapies. In this study, we show a 100-fold range in MIC frequency in human melanoma (1 in 18,000 to 1 in 1,851,000 cells) in the NOD/SCID mouse. In this model, human melanoma cells with high aldehyde dehydrogenase (ALDH) activity were enriched 16.8-fold in tumorigenic cells over unfractionated (UNF) cells, such that 1 in 21,000 cells was a MIC. In the NSG mouse, the ALDH expressing cell population was enriched 100-fold in tumorigenic cells over UNF cells, such that one in four cells was a MIC. Xenograft melanomas that developed from ALDH cells displayed robust self-renewal, whereas those from ALDH cells showed minimal self-renewal in vitro. Thus, ALDH melanoma cells have enhanced tumorigenicity over ALDH cells and superior self-renewal ability.
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U2 - 10.1038/jid.2010.237
DO - 10.1038/jid.2010.237
M3 - Article
AN - SCOPUS:78149469677
SN - 0022-202X
VL - 130
SP - 2799
EP - 2808
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 12
ER -